Substituted pyrrolidinones, their manufacture and their use as medicaments

ABSTRACT

The present invention relates to new substituted pyrrolidinones of general formula 
                         
wherein A, X, B and R 1  to R 9  are as defined above, or a tautomer or salt thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, which have valuable properties.

This application claims priority to German Application DE 10 2004 062544, filed on Dec. 24, 2004, which is incorporated herein in itsentirety.

The present invention relates to new substituted pyrrolidinones ofgeneral formula

the tautomers, the enantiomers, the diastereomers, the mixtures thereofand the salts thereof, particularly the physiologically acceptable saltsthereof with inorganic or organic acids or bases, which have valuableproperties.

The compounds of the above general formula I as well as the tautomers,the enantiomers, the diastereomers, the mixtures thereof and the saltsthereof, particularly the physiologically acceptable salts thereof withinorganic or organic acids or bases, and their stereoisomers havevaluable pharmacological properties, particularly an antithromboticactivity and a factor Xa-inhibiting activity.

The present application relates to new compounds of the above generalformula I, the preparation thereof, the pharmaceutical compositionscontaining the pharmacologically effective compounds, the preparationand use thereof.

A first embodiment of the present invention comprises those compounds ofgeneral formula I, wherein

A denotes a group of general formula

wherein

-   m is the number 1 or 2,-   R^(8a) in each case independently of one another denote a hydrogen    or halogen atom or a C₁₋₅-alkyl, hydroxy, hydroxy-C₁₋₅-alkyl,    C₁₋₅-alkoxy, C₁₋₅-alkoxy-C₁₋₅-alkyl, amino, C₁₋₅-alkylamino,    di-(C₁₋₅-alkyl)-amino, amino-C₁₋₅-alkyl, C₁₋₅-alkylamino-C₁₋₅-alkyl,    di-(C₁₋₅-alkyl)-amino-C₁₋₅-alkyl, aminocarbonyl,    C₁₋₅-alkylaminocarbonyl, di-(C₁₋₅-alkyl)-aminocarbonyl or    C₁₋₅-alkylcarbonylamino group, while    -   in the previously mentioned substituted 5- to 7-membered groups        A the heteroatoms F, Cl, Br, O, or N optionally introduced with        R^(8a) as substituents are not separated by precisely one carbon        atom from a heteroatom selected from among N, O and S,-   R^(8b) each independently of one another denote a hydrogen atom or a    C₁₋₅-alkyl group,-   R^(8c) each independently of one another denote a hydrogen atom, a    C₁₋₅-alkyl, C₁₋₅-alkylcarbonyl, C₁₋₅-alkyloxycarbonyl or    C₁₋₅-alkylsulphonyl group,-   X¹ denotes a carbonyl, thiocarbonyl, C═NR^(8c), C═N—OR^(8c),    C═N—NO₂, C═N—CN or sulphonyl group,-   X² denotes an oxygen atom or an —NR^(8b) group,-   X³ denotes a carbonyl, thiocarbonyl, C═NR^(8c), C═N—OR^(8c),    C═N—NO₂, C═N—CN or sulphonyl group,-   X⁴ denotes an oxygen or sulphur atom or an —NR^(8c) group,-   X⁵ denotes an oxygen atom or a —CH₂, —CHR^(8a) or —NR^(8c) group,-   X⁶ denotes a carbonyl or sulphonyl group,-   X⁷ denotes an oxygen atom, an —NR^(8b) or methylene group,-   R¹ denotes a hydrogen or halogen atom, a C₁₋₃-alkyl or C₁₋₃-alkoxy    group, while the hydrogen atoms of the C₁₋₃-alkyl or C₁₋₃-alkoxy    group may optionally be wholly or partly replaced by fluorine atoms,    a C₂₋₃-alkenyl, C₂₋₃-alkynyl, nitrile, nitro or amino group,-   R² denotes a hydrogen or halogen atom or a C₁₋₃-alkyl group,-   X denotes a nitrogen atom or a CH group,-   R³ denotes a hydrogen atom or a C₁₋₃-alkyl group,-   R⁴ and R⁵ each independently of one another denote    -   a hydrogen atom, a hydroxy group, an OR⁹ group, a C₂₋₆-alkenyl        or C₂₋₆-alkynyl group,    -   a straight-chain or branched C₁₋₆-alkyl group,        -   while the hydrogen atoms of the straight-chain or branched            C₁₋₆-alkyl group may optionally be wholly or partly replaced            by fluorine atoms, and which may optionally be substituted            by a C₃₋₅-cycloalkyl group, a nitrile, hydroxy, a            C₁₋₅-alkyloxy group, while the hydrogen atoms of the            C₁₋₅-alkyloxy group may optionally be wholly or partly            replaced by fluorine atoms, an allyloxy, propargyloxy,            benzyloxy, C₁₋₅-alkylcarbonyloxy, C₁₋₅-alkyloxycarbonyloxy,            carboxy-C₁₋₅-alkyloxy, C₁₋₅-alkyloxycarbonyl-C₁₋₅-alkyloxy,            mercapto, C₁₋₅-alkylsulphanyl, C₁₋₅-alkylsulphonyl, carboxy,            C₁₋₅-alkyloxycarbonyl, aminocarbonyl,            C₁₋₅-alkylaminocarbonyl, di-(C₁₋₅-alkyl)-aminocarbonyl,            C₃₋₆-cycloalkyleneiminocarbonyl, aminosulphonyl,            C₁₋₅-alkylaminosulphonyl, di-(C₁₋₅-alkyl)-aminosulphonyl,            C₃₋₆-cycloalkyleneiminosulphonyl, amino, C₁₋₅-alkylamino,            di-(C₁₋₅-alkyl)-amino, C₁₋₅-alkylcarbonylamino,            C₁₋₅-alkylsulphonylamino,            N-(C₁₋₅-alkylsulphonyl)-C₁₋₅-alkylamino or            C₃₋₆-cycloalkylcarbonylamino group,        -   while the 6- to 7-membered cyclic groups of the            C₃₋₆-cycloalkyleneiminocarbonyl group in the cyclic moiety a            methylene group in the 4 position of a 6- or 7-membered            cycloalkyleneimino group may be replaced by an oxygen or            sulphur atom, by a carbonyl, sulphinyl, sulphonyl or            —NR^(8c) group and additionally a methylene group adjacent            to an above-mentioned —NR^(8c) group may be replaced by a            carbonyl group,    -   a phenyl, or heteroaryl group        -   which may optionally be mono- to trisubstituted in the            phenyl or heteroaryl moiety by identical or different            substituents selected from among halogen atoms, C₁₋₅-alkyl,            di-(C₁₋₅-alkyl)-amino, hydroxy, C₁₋₅-alkyloxy, mono-, di- or            trifluoromethoxy, carboxy- and C₁₋₅-alkyloxycarbonyl groups,    -   a phenyl-C₁₋₅-alkyl or heteroaryl-C₁₋₅-alkyl group,        -   which may optionally be mono- to trisubstituted in the            phenyl or heteroaryl moiety by identical or different            substituents selected from among halogen atoms, C₁₋₅-alkyl,            di-(C₁₋₅-alkyl)-amino, hydroxy, C₁₋₅-alkyloxy, mono-, di- or            trifluoromethoxy, carboxy- and C₁₋₅-alkyloxycarbonyl groups,            and which may optionally be substituted in the            C₁₋₅-alkyl-moiety by a hydroxy, a C₁₋₅-alkyloxy group, while            the hydrogen atoms of the C₁₋₅-alkyloxy group may optionally            be wholly or partly replaced by fluorine atoms, an allyloxy,            propargyloxy, benzyloxy, C₁₋₅-alkylcarbonyloxy,            C₁₋₅-alkyloxycarbonyloxy, carboxy-C₁₋₅-alkyloxy, or a            C₁₋₅-alkyloxycarbonyl-C₁₋₅-alkyloxy group;    -   a 3- to 7-membered cycloalkyl, cycloalkyleneimino,        cycloalkyl-C₁₋₅-alkyl or cycloalkyleneimino-C₁₋₃-alkyl group,        -   wherein in 4- to 7-membered cyclic groups in the cyclic            moiety a methylene group may optionally be replaced by an            —N(R^(8c)) group, an oxygen or sulphur atom or a —S(O) or            —S(O)₂ group, or        -   wherein in 4- to 7-membered cyclic groups in the cyclic            moiety two adjacent methylene groups together may optionally            be replaced by a —C(O)N(R^(8b)) or —S(O)₂N(R^(8b)) group, or        -   wherein in 6- to 7-membered cyclic groups in the cyclic            moiety three adjacent methylene groups together may            optionally be replaced by a substituted —OC(O)N(R^(8b)) or            —N(R^(8b))C(O)N(R^(8b)) or —N(R^(8b))S(O)₂N(R^(8b)) group,        -   with the proviso that a 3- to 7-membered cycloalkyl,            cycloalkyleneimino, cycloalkyl-C₁₋₅-alkyl or            cycloalkyleneimino-C₁₋₃-alkyl group as hereinbefore defined            wherein two heteroatoms from the group oxygen and nitrogen            are separated from one another by precisely one optionally            substituted —CH₂ group, is excluded,        -   while a 3- to 7-membered cycloalkyl, cycloalkyleneimino,            cycloalkyl-C₁₋₅-alkyl or cycloalkyleneimino-C₁₋₃-alkyl group            as hereinbefore defined may be substituted at one or two            —CH₂ groups by one or two C₁₋₃-alkyl groups in each case,    -   with the proviso that R⁴ and R⁵ may not simultaneously be        defined as hydroxy or OR⁹ groups, or-   R⁴ and R⁵ together with the carbon atom to which they are bound form    a C₃₋₈-cycloalkyl or C₃₋₈-cycloalkenyl group,    -   while one of the methylene groups of a C₄₋₈-cycloalkyl group may        be replaced by an oxygen or sulphur atom or an —N(R^(8c)), or a        carbonyl, sulphinyl or sulphonyl group, and/or    -   two directly adjacent methylene groups of a C₄₋₈-cycloalkyl        group may together be replaced by a —C(O)N(R^(8b)) or        —S(O)₂N(R^(8b)) group, and/or    -   three directly adjacent methylene groups of a C₆₋₈-cycloalkyl        group may together be replaced by a —OC(O)N(R^(8b)),        —N(R^(8b))C(O)N(R^(8b)) or —N(R^(8b))S(O)₂N(R^(8b)) group,    -   while 1 to 3 carbon atoms of a C₃₋₈-cycloalkyl group may        optionally be substituted independently of one another by in        each case one or two identical or different halogen atoms or        C₁₋₅-alkyl, nitrile, hydroxy, C₁₋₅-alkyloxy,        C₁₋₅-alkylcarbonyloxy, carboxy-C₁₋₅-alkyl,        C₁₋₅-alkyloxycarbonyl-C₁₋₅-alkyl, C₁₋₅-alkylsulphanyl,        C₁₋₅-alkylsulphonyl, carboxy, C₁₋₅-alkyloxycarbonyl,        aminocarbonyl, C₁₋₅-alkylaminocarbonyl,        di-(C₁₋₅-alkyl)-aminocarbonyl, C₃₋₆-cycloalkyleneiminocarbonyl,        aminosulphonyl, C₁₋₅-alkylaminosulphonyl,        di-(C₁₋₅-alkyl)-aminosulphonyl,        C₃₋₆-cycloalkyleneiminosulphonyl, amino, C₁₋₅-alkylamino,        di-(C₁₋₅-alkyl)-amino, C₁₋₅-alkylcarbonylamino,        C₁₋₅-alkyl-sulphonylamino,        N-(C₁₋₅-alkylsulphonyl)-C₁₋₅-alkylamino or        C₃₋₆-cycloalkylcarbonylamino groups,    -   while 1 to 2 carbon atoms of a C₃₋₈-cycloalkenyl group may        optionally be substituted independently of one another by in        each case a C₁₋₅-alkyl, nitrile, carboxy-C₁₋₅-alkyl,        C₁₋₅-alkyloxycarbonyl-C₁₋₅-alkyl, carboxy,        C₁₋₅-alkyloxycarbonyl, aminocarbonyl, C₁₋₅-alkylaminocarbonyl,        di-(C₁₋₅-alkyl)-aminocarbonyl, C₃₋₆-cycloalkyleneiminocarbonyl,        aminosulphonyl, C₁₋₅-alkylaminosulphonyl,        di-(C₁₋₅-alkyl)-aminosulphonyl, C₃₋₆-cycloalkyleneiminosulphonyl        groups,    -   and 1 to 2 carbon atoms of a C₄₋₈-cycloalkenyl group which are        not bound by a double bond to another carbon atom, may        optionally be substituted independently of one another by a        fluorine atom or a hydroxy, C₁₋₅-alkyloxy,        C₁₋₅-alkylcarbonyloxy, C₁₋₅-alkylsulphanyl, C₁₋₅-alkylsulphonyl,        amino, C₁₋₅-alkylamino, di-(C₁₋₅-alkyl)-amino,        C₁₋₅-alkylcarbonylamino, C₁₋₅-alkylsulphonylamino,        N-(C₁₋₅-alkylsulphonyl)-C₁₋₅-alkylamino or        C₃₋₆-cycloalkylcarbonyl-amino groups,    -   with the proviso that a C₃₋₈-cycloalkyl or C₃₋₈-cycloalkenyl        group of this kind formed from R⁴ and R⁵ together,        -   wherein two heteroatoms in the cyclic group selected from            among oxygen and nitrogen are separated from one another by            precisely one optionally substituted —CH₂ group, and/or        -   wherein one or both methylene groups of the cyclic group,            which are directly attached to the carbon atom to which the            groups R⁴ and R⁵ are bound, are replaced by a heteroatom            selected from among oxygen, nitrogen and sulphur, and/or        -   wherein a substituent bound to the cyclic group, which is            characterised in that a heteroatom selected from among            oxygen, nitrogen, sulphur and halogen atom is bound directly            to the cyclic group, is separated from another heteroatom            selected from among oxygen, nitrogen and sulphur, with the            exception of the sulphone group, by precisely one optionally            substituted methylene group, and/or        -   wherein two oxygen atoms are joined together directly,    -   is excluded,-   R⁹ denotes a straight-chain or branched C₁₋₆-alkyl group,    -   while the hydrogen atoms of the straight-chain or branched        C₁₋₆-alkyl group may optionally be wholly or partly replaced by        fluorine atoms, and which may optionally be substituted by a        C₃₋₅-cycloalkyl group, a hydroxy, a C₁₋₅-alkyloxy group, while        the hydrogen atoms of the C₁₋₅-alkyloxy group may optionally be        wholly or partly replaced by fluorine atoms, an allyloxy,        propargyloxy, benzyloxy, C₁₋₅-alkylcarbonyloxy,        C₁₋₅-alkyloxycarbonyloxy, carboxy-C₁₋₅-alkyloxy,        C₁₋₅-alkyloxycarbonyl-C₁₋₅-alkyloxy, carboxy,        C₁₋₅-alkyloxycarbonyl, aminocarbonyl, C₁₋₅-alkylaminocarbonyl,        di-(C₁₋₅-alkyl)-aminocarbonyl, C₃₋₆-cycloalkyleneiminocarbonyl,        amino, C₁₋₅-alkylamino, di-(C₁₋₅-alkyl)-amino,        C₁₋₅-alkylcarbonylamino, C₁₋₅-alkylsulphonylamino,        N-(C₁₋₅-alkylsulphonyl)-C₁₋₅-alkylamino or        C₃₋₆-cycloalkylcarbonylamino group,        -   while the 6- to 7-membered cyclic groups of the            C₃₋₆-cycloalkyleneiminocarbonyl group in the cyclic moiety a            methylene group in the 4 position of a 6- or 7-membered            cycloalkyleneimino group may be replaced by an oxygen or            sulphur atom, by a carbonyl, sulphinyl, sulphonyl or            —NR^(8c) group and additionally a methylene group adjacent            to an above-mentioned —NR^(8c) group may be replaced by a            carbonyl group,    -   with the proviso that the replacement of hydrogen atoms of the        first carbon atom of the straight-chain or branched C₁₋₆-alkyl        group by substituents from the group comprising oxygen, sulphur        or nitrogen is excluded,    -   a phenyl, heteroaryl, phenyl-C₁₋₅-alkyl or heteroaryl-C₁₋₅-alkyl        group, which may optionally be mono- to trisubstituted in the        phenyl or heteroaryl moiety by identical or different        substituents selected from among halogen atoms, C₁₋₅-alkyl,        di-(C₁₋₅-alkyl)-amino, hydroxy, C₁₋₅-alkyloxy, mono-, di- or        trifluoromethoxy, carboxy- and C₁₋₅-alkyloxycarbonyl groups,    -   a 3- to 7-membered cycloalkyl, cycloalkyl-C₁₋₅-alkyl or        cycloalkyleneimino-C₂₋₃-alkyl group,        -   wherein in 4- to 7-membered cyclic groups in the cyclic            moiety a methylene group may optionally be replaced by an            —N(R^(8c)) group, an oxygen or sulphur atom or a —S(O) or            —S(O)₂ group, or        -   wherein in 4- to 7-membered cyclic groups in the cyclic            moiety two adjacent methylene groups together may optionally            be replaced by a —C(O)N(R^(8b)) or —S(O)₂N(R^(8b)) group, or        -   wherein in 6- to 7-membered cyclic groups in the cyclic            moiety three adjacent methylene groups together may            optionally be replaced by a substituted —OC(O)N(R^(8b)) or            —N(R^(8b))C(O)N(R^(8b)) or —N(R^(8b))S(O)₂N(R^(8b)) group,            -   with the proviso that a 3- to 7-membered cycloalkyl,                cycloalkyl-C₁₋₅-alkyl or cycloalkyleneimino-C₂₋₃-alkyl                group as hereinbefore defined wherein two heteroatoms                from the group comprising oxygen and nitrogen are                separated from one another by precisely one optionally                substituted —CH₂ group, is excluded,            -   while a 3- to 7-membered cycloalkyl,                cycloalkyl-C₁₋₅-alkyl or cycloalkyleneimino-C₂₋₃-alkyl                group as hereinbefore defined may be substituted at one                or two —CH₂ groups by one or two C₁₋₃-alkyl groups in                each case,-   B denotes a group of general formula

-   Y denotes a nitrogen atom or a CH group,-   R⁶ denotes a hydrogen, a halogen atom, a nitrile group, a    C₂₋₃-alkenyl, C₂₋₃-alkynyl, a C₁₋₃-alkyl group, or a C₁₋₃-alkoxy    group, while the hydrogen atoms of the C₁₋₃-alkyl or C₁₋₃-alkoxy    group may optionally be wholly or partly replaced by fluorine atoms,    while, unless otherwise stated, by the term “heteroaryl group”    mentioned hereinbefore in the definitions is meant a monocyclic 5-    or 6-membered heteroaryl group, while    -   the 6-membered heteroaryl group contains one, two or three        nitrogen atoms and    -   the 5-membered heteroaryl group contains an imino group        optionally substituted by a C₁₋₃-alkyl, phenyl or        phenyl-C₁₋₃-alkyl group, or an oxygen or sulphur atom or    -   an imino group optionally substituted by a C₁₋₃-alkyl, phenyl,        amino-C₂₋₃-alkyl, C₁₋₃-alkylamino-C₂₋₃-alkyl,        di-(C₁₋₃-alkyl)-amino-C₂₋₃-alkyl, a        C₃₋₆-cycloalkyleneimino-C₁₋₃-alkyl or phenyl-C₁₋₃-alkyl group,        or an oxygen or sulphur atom and additionally a nitrogen atom or    -   an imino group optionally substituted by a C₁₋₃-alkyl or        phenyl-C₁₋₃-alkyl group and two or three nitrogen atoms,    -   and moreover a phenyl ring optionally substituted by a fluorine,        chlorine or bromine atom, a C₁₋₃-alkyl, hydroxy, C₁₋₃-alkyloxy        group, amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino or        C₃₋₆-cycloalkyleneimino group may be fused to the        above-mentioned monocyclic heteroaryl groups via two adjacent        carbon atoms    -   and the bond is effected via a nitrogen atom or a carbon atom of        the heterocyclic moiety or a fused-on phenyl ring,        while, unless otherwise stated, by the term “halogen atom”        mentioned hereinbefore in the definitions is meant an atom        selected from among fluorine, chlorine, bromine and iodine,        while the alkyl, alkenyl, alkynyl and alkoxy groups contained in        the above-mentioned definitions which have more than two carbon        atoms may, unless otherwise stated, be straight-chain or        branched and the alkyl groups in the previously mentioned        dialkylated groups, for example the dialkylamino groups, may be        identical or different,

and the hydrogen atoms of the methyl or ethyl groups contained in theforegoing definitions, unless otherwise stated, may be wholly or partlyreplaced by fluorine atoms,

the tautomers, the enantiomers, the diastereomers, the mixtures thereofand the salts thereof.

A second embodiment of the present invention includes those compounds ofgeneral formula I, wherein

A denotes a group of general formula

wherein

-   m is the number 1 or 2,-   R^(8a) each independently of one another denote a hydrogen or    halogen atom or a C₁₋₅-alkyl, hydroxy, hydroxy-C₁₋₅-alkyl,    C₁₋₅-alkoxy, C₁₋₅-alkoxy-C₁₋₅-alkyl, amino, C₁₋₅-alkylamino,    di-(C₁₋₅-alkyl)-amino, amino-C₁₋₅-alkyl, C₁₋₅-alkylamino-C₁₋₅-alkyl,    di-(C₁₋₅-alkyl)-amino-C₁₋₅-alkyl, aminocarbonyl,    C₁₋₅-alkylaminocarbonyl, di-(C₁₋₅-alkyl)-aminocarbonyl or    C₁₋₅-alkylcarbonylamino group denotes, while in the previously    mentioned substituted 5- to 7-membered groups A the heteroatoms F,    Cl, Br, I, O or N optionally introduced with R^(8a) as substituents    are not separated by precisely one carbon atom from a heteroatom    selected from among N, O and S,-   R^(8b) each independently of one another denote a hydrogen atom or a    C₁₋₅-alkyl group,-   R^(8c) each independently of one another denote a hydrogen atom, a    C₁₋₅-alkyl, C₁₋₅-alkylcarbonyl, C₁₋₅-alkyloxycarbonyl or    C₁₋₅-alkylsulphonyl group,-   X¹ denotes a carbonyl, thiocarbonyl, C═NR^(8c), C═N—OR^(8c),    C═N—NO₂, C═N—CN or sulphonyl group,-   X² denotes an oxygen atom or an —NR^(8b) group,-   X³ denotes a carbonyl, thiocarbonyl, C═NR^(8c), C═N—OR^(8c),    C═N—NO₂, C═N—CN or sulphonyl group,-   X⁴ denotes an oxygen or sulphur atom or an —NR^(8c) group,-   X⁵ denotes an oxygen atom or a —CH₂, —CHR^(8a) or —NR^(8c) group,-   X⁶ denotes a carbonyl or sulphonyl group,-   R¹ denotes a hydrogen or halogen atom, a C₁₋₃-alkyl or C₁₋₃-alkoxy    group, while the hydrogen atoms of the C₁₋₃-alkyl or C₁₋₃-alkoxy    group may optionally be wholly or partly replaced by fluorine atoms,    a C₂₋₃-alkenyl, C₂₋₃-alkynyl, nitrile, nitro or amino group,-   R² denotes a hydrogen or halogen atom or a C₁₋₃-alkyl group,-   X denotes a nitrogen atom or a CH group,-   R³ denotes a hydrogen atom or a C₁₋₃-alkyl group,-   R⁴ and R⁵ each independently of one another denote    -   a hydrogen atom, a hydroxy group, a OR⁹ group, a C₂₋₆-alkenyl or        C₂₋₆-alkynyl group,    -   a straight-chain or branched C₁₋₆-alkyl group,        -   while the hydrogen atoms of the straight-chain or branched            C₁₋₆-alkyl group may optionally be wholly or partly replaced            by fluorine atoms, and which may optionally be substituted            by a C₃₋₅-cycloalkyl group, a nitrile, hydroxy, a            C₁₋₅-alkyloxy group, while the hydrogen atoms of the            C₁₋₅-alkyloxy group may optionally be wholly or partly            replaced by fluorine atoms, an allyloxy, propargyloxy,            benzyloxy, C₁₋₅-alkylcarbonyloxy, C₁₋₅-alkyloxycarbonyloxy,            carboxy-C₁₋₅-alkyloxy, C₁₋₅-alkyloxycarbonyl-C₁₋₅-alkyloxy,            mercapto, C₁₋₅-alkylsulphanyl, C₁₋₅-alkylsulphonyl, carboxy,            C₁₋₅-alkyloxycarbonyl, aminocarbonyl,            C₁₋₅-alkylaminocarbonyl, di-(C₁₋₅-alkyl)-aminocarbonyl,            C₃₋₆-cycloalkyleneiminocarbonyl, aminosulphonyl,            C₁₋₅-alkylaminosulphonyl, di-(C₁₋₅-alkyl)-aminosulphonyl,            C₃₋₆-cycloalkyleneiminosulphonyl, amino, C₁₋₅-alkylamino,            di-(C₁₋₅-alkyl)-amino, C₁₋₅-alkylcarbonylamino,            C₁₋₅-alkylsulphonylamino,            N-(C₁₋₅-alkylsulphonyl)-C₁₋₅-alkylamino or            C₃₋₆-cycloalkylcarbonylamino group,        -   while the 6- to 7-membered cyclic groups of the            C₃₋₆-cycloalkyleneiminocarbonyl group in the cyclic moiety a            methylene group in the 4 position of a 6- or 7-membered            cycloalkyleneimino group may be replaced by an oxygen or            sulphur atom, by a carbonyl, sulphinyl, sulphonyl or            —NR^(8c) group and additionally a methylene group adjacent            to an above-mentioned —NR^(8c) group may be replaced by a            carbonyl group,    -   a phenyl or heteroaryl group        -   which may optionally be mono- to trisubstituted in the            phenyl or heteroaryl moiety by identical or different            substituents selected from among halogen atoms, C₁₋₅-alkyl,            di-(C₁₋₅-alkyl)-amino, hydroxy, C₁₋₅-alkyloxy, mono-, di- or            trifluoromethoxy, carboxy- and C₁₋₅-alkyloxycarbonyl groups,    -   a phenyl-C₁₋₅-alkyl or heteroaryl-C₁₋₅-alkyl group,        -   which may optionally be mono- to trisubstituted in the            phenyl or heteroaryl moiety by identical or different            substituents selected from among halogen atoms, C₁₋₅-alkyl,            di-(C₁₋₅-alkyl)-amino, hydroxy, C₁₋₅-alkyloxy, mono-, di- or            trifluoromethoxy, carboxy- and C₁₋₅-alkyloxycarbonyl groups,            and which may optionally be substituted in the            C₁₋₅-alkyl-moiety by a hydroxy, a C₁₋₅-alkyloxy group, while            the hydrogen atoms of the C₁₋₅-alkyloxy group may optionally            be wholly or partly replaced by fluorine atoms, an allyloxy,            propargyloxy, benzyloxy, C₁₋₅-alkylcarbonyloxy,            C₁₋₅-alkyloxycarbonyloxy, carboxy-C₁₋₅-alkyloxy, or a            C₁₋₅-alkyloxycarbonyl-C₁₋₅-alkyloxy group;    -   a 3- to 7-membered cycloalkyl, cycloalkyleneimino,        cycloalkyl-C₁₋₅-alkyl or cycloalkyleneimino-C₁₋₃-alkyl group,        -   wherein in 4- to 7-membered cyclic groups in the cyclic            moiety a methylene group may optionally be replaced by an            —N(R^(8c)) group, an oxygen or sulphur atom or a —S(O) or            —S(O)₂ group, or        -   wherein in 4- to 7-membered cyclic groups in the cyclic            moiety two adjacent methylene groups together may optionally            be replaced by a —C(O)N(R^(8b)) or —S(O)₂N(R^(8b)) group, or        -   wherein in 6- to 7-membered cyclic groups in the cyclic            moiety three adjacent methylene groups together may            optionally be replaced by a substituted —OC(O)N(R^(8b)) or            —N(R^(8b))C(O)N(R^(8b)) or —N(R ^(8b))S(O)₂N(R^(8b)) group,        -   with the proviso that a 3- to 7-membered cycloalkyl,            cycloalkyleneimino, cycloalkyl-C₁₋₅-alkyl or            cycloalkyleneimino-C₁₋₃-alkyl group as hereinbefore defined            wherein two heteroatoms from the group comprising oxygen and            nitrogen are separated from one another by precisely one            optionally substituted —CH₂ group, is excluded,        -   while a 3- to 7-membered cycloalkyl, cycloalkyleneimino,            cycloalkyl-C₁₋₅-alkyl or cycloalkyleneimino-C₁₋₃-alkyl group            as hereinbefore defined may be substituted at one or two            —CH₂ groups by one or two C₁₋₃-alkyl groups in each case,    -   with the proviso that R⁴ and R⁵ cannot simultaneously be defined        as hydroxy or OR⁹ groups, or-   R⁴ and R⁵ together with the carbon atom to which they are bound form    a C₃₋₈-cycloalkyl or C₃₋₈-cycloalkenyl group,    -   while one of the methylene groups of a C₄₋₈-cycloalkyl group may        be replaced by an oxygen or sulphur atom or an —N(R^(8c)), or a        carbonyl, sulphinyl or sulphonyl group, and/or    -   two directly adjacent methylene groups of a C₄₋₈-cycloalkyl        group may together be replaced by a —C(O)N(R^(8b)) or        —S(O)₂N(R^(8b)) group, and/or    -   three directly adjacent methylene groups of a C₆₋₈-cycloalkyl        group may together be replaced by a —OC(O)N(R^(8b)),        —N(R^(8b))C(O)N(R^(8b)) or —N(R^(8b))S(O)₂N(R^(8b)) group,    -   while 1 to 3 carbon atoms of a C₃₋₈-cycloalkyl group may        optionally be substituted independently of one another by in        each case one or two identical or different halogen atoms or        C₁₋₅-alkyl, nitrile, hydroxy, C₁₋₅-alkyloxy,        C₁₋₅-alkylcarbonyloxy, carboxy-C₁₋₅-alkyl,        C₁₋₅-alkyloxycarbonyl-C₁₋₅-alkyl, C₁₋₅-alkylsulphanyl,        C₁₋₅-alkylsulphonyl, carboxy, C₁₋₅-alkyloxycarbonyl,        aminocarbonyl, C₁₋₅-alkylaminocarbonyl,        di-(C₁₋₅-alkyl)-aminocarbonyl, C₃₋₆-cycloalkyleneiminocarbonyl,        aminosulphonyl, C₁₋₅-alkylaminosulphonyl,        di-(C₁₋₅-alkyl)-aminosulphonyl,        C₃₋₆-cycloalkyleneiminosulphonyl, amino, C₁₋₅-alkylamino,        di-(C₁₋₅-alkyl)-amino, C₁₋₅-alkylcarbonylamino,        C₁₋₅-alkyl-sulphonylamino,        N-(C₁₋₅-alkylsulphonyl)-C₁₋₅-alkylamino or        C₃₋₆-cycloalkylcarbonylamino groups,    -   while 1 to 2 carbon atoms of a C₃₋₈-cycloalkenyl group may        optionally be substituted independently of one another by in        each case a C₁₋₅-alkyl, nitrile, carboxy-C₁₋₅-alkyl,        C₁₋₅-alkyloxycarbonyl-C₁₋₅-alkyl, carboxy,        C₁₋₅-alkyloxycarbonyl, aminocarbonyl, C₁₋₅-alkylaminocarbonyl,        di-(C₁₋₅-alkyl)-aminocarbonyl, C₃₋₆-cycloalkyleneiminocarbonyl,        aminosulphonyl, C₁₋₅-alkylaminosulphonyl,        di-(C₁₋₅-alkyl)-aminosulphonyl, C₃₋₆-cycloalkyleneiminosulphonyl        groups,    -   and 1 to 2 carbon atoms of a C₄₋₈-cycloalkenyl group which are        not bound by a double bond to another carbon atom may optionally        be substituted independently of one another by a fluorine atom        or a hydroxy, C₁₋₅-alkyloxy, C₁₋₅-alkylcarbonyloxy,        C₁₋₅-alkylsulphanyl, C₁₋₅-alkylsulphonyl, amino,        C₁₋₅-alkylamino, di-(C₁₋₅-alkyl)-amino, C₁₋₅-alkylcarbonylamino,        C₁₋₅-alkylsulphonylamino,        N-(C₁₋₅-alkylsulphonyl)-C₁₋₅-alkylamino or        C₃₋₆-cycloalkylcarbonyl-amino groups,    -   with the proviso that a C₃₋₈-cycloalkyl or C₃₋₈-cycloalkenyl        group of this kind formed from R⁴ and R⁵ together,        -   wherein two heteroatoms in the cyclic group selected from            among oxygen and nitrogen are separated from one another by            precisely one optionally substituted —CH₂ group, and/or        -   wherein one or both methylene groups of the cyclic group,            which are directly attached to the carbon atom to which the            groups R⁴ and R⁵ are bound, are replaced by a heteroatom            from the group comprising oxygen, nitrogen and sulphur,            and/or        -   wherein a substituent bound to the cyclic group, which is            characterised in that a heteroatom selected from among            oxygen, nitrogen, sulphur and halogen atom is bound directly            to the cyclic group, is separated from another heteroatom            selected from among oxygen, nitrogen and sulphur, with the            exception of the sulphone group, by precisely one,            optionally substituted methylene group, and/or        -   wherein two oxygen atoms are joined together directly,    -   is excluded,-   R⁹ denotes a straight-chain or branched C₁₋₆-alkyl group,    -   while the hydrogen atoms of the straight-chain or branched        C₁₋₆-alkyl group may optionally be wholly or partly replaced by        fluorine atoms, and which may optionally be substituted by a        C₃₋₅-cycloalkyl group, a hydroxy, a C₁₋₅-alkyloxy group, while        the hydrogen atoms of the C₁₋₅-alkyloxy group may optionally be        wholly or partly replaced by fluorine atoms, an allyloxy,        propargyloxy, benzyloxy, C₁-₅-alkylcarbonyloxy,        C₁₋₅-alkyloxycarbonyloxy, carboxy-C₁₋₅-alkyloxy,        C₁₋₅-alkyloxycarbonyl-C₁₋₅-alkyloxy, carboxy,        C₁₋₅-alkyloxycarbonyl, aminocarbonyl, C₁₋₅-alkylaminocarbonyl,        di-(C₁₋₅-alkyl)-aminocarbonyl, C₃₋₆-cycloalkyleneiminocarbonyl,        amino, C₁₋₅-alkylamino, di-(C₁₋₅-alkyl)-amino,        C₁₋₅-alkylcarbonylamino, C₁₋₅-alkylsulphonylamino,        N-(C₁₋₅-alkylsulphonyl)-C₁₋₅-alkylamino or        C₃₋₆-cycloalkylcarbonylamino group,        -   while the 6- to 7-membered cyclic groups of the            C₃₋₆-cycloalkyleneiminocarbonyl group in the cyclic moiety a            methylene group in the 4 position of a 6- or 7-membered            cycloalkyleneimino group may be replaced by an oxygen or            sulphur atom, by a carbonyl, sulphinyl, sulphonyl or            —NR^(8c) group and additionally a methylene group adjacent            to an above-mentioned —NR^(8c) group may be replaced by a            carbonyl group,    -   with the proviso that the replacement of hydrogen atoms of the        first carbon atom of the straight-chain or branched C₁₋₆-alkyl        group by substituents from the group comprising oxygen, sulphur        or nitrogen is excluded,    -   a phenyl, heteroaryl, phenyl-C₁₋₅-alkyl or heteroaryl-C₁₋₅-alkyl        group,        -   which may optionally be mono- to trisubstituted in the            phenyl or heteroaryl moiety by identical or different            substituents selected from among halogen atoms, C₁₋₅-alkyl,            di-(C₁₋₅-alkyl)-amino, hydroxy, C₁₋₅-alkyloxy, mono-, di- or            trifluoromethoxy, carboxy- and C₁₋₅-alkyloxycarbonyl groups,    -   a 3- to 7-membered cycloalkyl, cycloalkyl-C₁₋₅-alkyl or        cycloalkyleneimino-C₂₋₃-alkyl group,        -   wherein in 4- to 7-membered cyclic groups in the cyclic            moiety a methylene group may optionally be replaced by an            —N(R⁸c) group, an oxygen or sulphur atom or a —S(O) or            —S(O)₂ group, or        -   wherein in 4- to 7-membered cyclic groups in the cyclic            moiety two adjacent methylene groups together may optionally            be replaced by a —C(O)N(R^(8b)) or —S(O)₂N(R^(8b)) group, or        -   wherein in 6- to 7-membered cyclic groups in the cyclic            moiety three adjacent methylene groups together may            optionally be replaced by a substituted —OC(O)N(R^(8b)) or            —N(R^(8b))C(O)N(R^(8b)) or —N(R^(8b))S(O)₂N(R^(8b)) group,        -   with the proviso that a 3- to 7-membered cycloalkyl,            cycloalkyl-C₁₋₅-alkyl or cycloalkyleneimino-C₂₋₃-alkyl group            as hereinbefore defined wherein two heteroatoms from the            group comprising oxygen and nitrogen are separated from one            another by precisely one optionally substituted —CH₂ group,            is excluded,        -   while a 3- to 7-membered cycloalkyl, cycloalkyl-C₁₋₅-alkyl            or cycloalkyleneimino-C₂₋₃-alkyl group as hereinbefore            defined may be substituted at one or two —CH₂ groups by one            or two C₁₋₃-alkyl groups in each case,

B denotes a group of general formula

-   Y denotes a nitrogen atom or a CH group,-   R⁶ denotes a hydrogen, a halogen atom, a nitrile group, a    C₂₋₃-alkenyl, C₂₋₃-alkynyl, a C₁₋₃-alkyl group, or a C₁₋₃-alkoxy    group, while the hydrogen atoms of the C₁₋₃-alkyl or C₁₋₃-alkoxy    group may optionally be wholly or partly replaced by fluorine atoms,    while, unless otherwise stated, by the term “heteroaryl group”    mentioned hereinbefore in the definitions is meant a monocyclic 5-    or 6-membered heteroaryl group, while    -   the 6-membered heteroaryl group contains one, two or three        nitrogen atoms and    -   the 5-membered heteroaryl group contains an imino group        optionally substituted by a C₁₋₃-alkyl, phenyl or        phenyl-C₁₋₃-alkyl group, or an oxygen or sulphur atom or    -   an imino group optionally substituted by a C₁₋₃-alkyl, phenyl,        amino-C₂₋₃-alkyl, C₁₋₃-alkylamino-C₂₋₃-alkyl,        di-(C₁₋₃-alkyl)-amino-C₂₋₃-alkyl, a        C₃₋₆-cycloalkyleneimino-C₁₋₃-alkyl or phenyl-C₁₋₃-alkyl group,        or an oxygen or sulphur atom and additionally a nitrogen atom or    -   an imino group optionally substituted by a C₁₋₃-alkyl or        phenyl-C₁₋₃-alkyl group and two or three nitrogen atoms,    -   and moreover a phenyl ring optionally substituted by a fluorine,        chlorine or bromine atom, a C₁₋₃-alkyl, hydroxy, C₁₋₃-alkyloxy        group, amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino or        C₃₋₆-cycloalkyleneimino group may be fused to the        above-mentioned monocyclic heteroaryl groups via two adjacent        carbon atoms    -   and the bond is effected via a nitrogen atom or a carbon atom of        the heterocyclic moiety or a fused-on phenyl ring,        while, unless otherwise stated, by the term “halogen atom”        mentioned hereinbefore in the definitions is meant an atom        selected from among fluorine, chlorine, bromine and iodine,        while the alkyl, alkenyl, alkynyl and alkoxy groups contained in        the above-mentioned definitions which have more than two carbon        atoms, unless otherwise stated, may be straight-chain or        branched and the alkyl groups in the previously mentioned        dialkylated groups, for example the dialkylamino groups, may be        identical or different,        and the hydrogen atoms of the methyl or ethyl groups contained        in the foregoing definitions, unless otherwise stated, may be        wholly or partly replaced by fluorine atoms,        the tautomers, the enantiomers, the diastereomers, the mixtures        thereof and the salts thereof.

A third embodiment of the present invention includes those compounds ofgeneral formula I, wherein

A denotes a group of general formula

wherein

-   m is the number 1 or 2,-   R^(8a) each independtnly of one another dneote a hydrogen pr    fluorine atom or a C₁₋₃-alkyl, hydroxy, hydroxy-C₁₋₃-alkyl,    C₁₋₃-alkoxy, C₁₋₃-alkoxy-C₁₋₃-alkyl, amino, C₁₋₃-alkylamino,    di-(C₁₋₃-alkyl)-amino, amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl,    or di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl group, while in the previously    mentioned substituted 5- to 7-membered groups A the heteroatoms F, O    or N optionally introduced with R^(8a) as substituents are not    separated by precisely one carbon atom from a heteroatom selected    from among N, O and S,-   R^(8b) each independently of one another denote a hydrogen atom or a    C₁₋₃-alkyl group,-   R^(8c) each independently of one another denote a hydrogen atom, a    C₁₋₃-alkyl, C₁₋₃-alkylcarbonyl, C₁₋₃-alkyloxycarbonyl or    C₁₋₃-alkylsulphonyl group,-   X¹ denotes a carbonyl, thiocarbonyl, C═NR^(8c), C═N—OR^(8c),    C═N—NO₂, C═N—CN or sulphonyl group,-   X² denotes an oxygen atom or an —NR^(8b) group,-   X³ denotes a carbonyl, thiocarbonyl, C═NR^(8c), C═N—OR^(8c),    C═N—NO₂, C═N—CN or sulphonyl group,-   X⁴ denotes an oxygen or sulphur atom or an —NR^(8c) group,-   X⁵ denotes an oxygen atom or a —CH₂, —CHR^(8a) or —NR^(8c) group,-   X⁶ denotes a carbonyl or sulphonyl group,-   R¹ denotes a hydrogen or halogen atom, a C₁₋₃-alkyl or C₁₋₃-alkoxy    group, while the hydrogen atoms of the C₁₋₃-alkyl or C₁₋₃-alkoxy    group may optionally be wholly or partly replaced by fluorine atoms,    a C₂₋₃-alkenyl, C₂₋₃-alkynyl, nitrile, nitro or amino group,-   R² denotes a hydrogen or halogen atom or a methyl group,-   X denotes a nitrogen atom or a CH group,-   R³ denotes a hydrogen atom or a C₁₋₃-alkyl group,-   R⁴ and R⁵ each independently of one another denote    -   a hydrogen atom, a hydroxy group, a OR⁹ group, a C₂₋₆-alkenyl or        C₂₋₆-alkynyl group,    -   a straight-chain or branched C₁₋₆-alkyl group,        -   while the hydrogen atoms of the straight-chain or branched            C₁₋₆-alkyl group may optionally be wholly or partly replaced            by fluorine atoms, and which may optionally be substituted            by a C₃₋₅-cycloalkyl group, a nitrile, hydroxy, a            C₁₋₅-alkyloxy group, while the hydrogen atoms of the            C₁₋₅-alkyloxy group may optionally be wholly or partly            replaced by fluorine atoms, an allyloxy, propargyloxy,            benzyloxy, C₁₋₅-alkylcarbonyloxy, C₁₋₅-alkyloxycarbonyloxy,            carboxy-C₁ ₅-alkyloxy, C₁₋₅-alkyloxycarbonyl-C₁₋₅-alkyloxy,            mercapto, C₁₋₅-alkylsulphanyl, C₁₋₅-alkylsulphonyl, carboxy,            C₁₋₅-alkyloxycarbonyl, aminocarbonyl,            C₁₋₅-alkylaminocarbonyl, di-(C₁₋₅-alkyl)-aminocarbonyl,            C₃₋₆-cycloalkyleneiminocarbonyl, aminosulphonyl,            C₁₋₅-alkylaminosulphonyl, di-(C₁₋₅-alkyl)-aminosulphonyl,            C₃₋₆-cycloalkyleneiminosulphonyl, amino, C₁₋₅-alkylamino,            di-(C₁₋₅-alkyl)-amino, C₁₋₅-alkylcarbonylamino,            C₁₋₅-alkylsulphonylamino,            N-(C₁₋₅-alkylsulphonyl)-C₁₋₅-alkylamino or            C₃₋₆-cycloalkylcarbonylamino group,            -   while the 6- to 7-membered cyclic groups of the                C₃₋₆-cycloalkyleneiminocarbonyl group in the cyclic                moiety a methylene group in the 4 position of a 6- or                7-membered cycloalkyleneimino group may be replaced by                an oxygen or sulphur atom, by a carbonyl, sulphinyl,                sulphonyl or —NR^(8c) group and additionally a methylene                group adjacent to an above-mentioned —NR^(8c) group may                be replaced by a carbonyl group,    -   a phenyl, heteroaryl, phenyl-C₁₋₅-alkyl or heteroaryl-C₁₋₅-alkyl        group,        -   which may optionally be mono- to trisubstituted in the            phenyl or heteroaryl moiety by identical or different            substituents selected from among halogen atoms, C₁₋₅-alkyl,            di-(C₁₋₅-alkyl)-amino, hydroxy, C₁₋₅-alkyloxy, mono-, di- or            trifluoromethoxy, carboxy- and C₁₋₅-alkyloxycarbonyl groups,    -   a 3- to 7-membered cycloalkyl, cycloalkyleneimino,        cycloalkyl-C₁₋₅-alkyl or cycloalkyleneimino-C₁₋₃-alkyl group,        -   wherein in 4- to 7-membered cyclic groups in the cyclic            moiety a methylene group may optionally be replaced by an            —N(R^(8c)) group, an oxygen or sulphur atom or a —S(O) or            —S(O)₂ group, or        -   wherein in 4- to 7-membered cyclic groups in the cyclic            moiety two adjacent methylene groups together may optionally            be replaced by a —C(O)N(R^(8b)) or —S(O)₂N(R^(8b)) group, or        -   wherein in 6- to 7-membered cyclic groups in the cyclic            moiety three adjacent methylene groups together may            optionally be replaced by a substituted —OC(O)N(R^(8b)) or            —N(R^(8b))C(O)N(R^(8b)) or —N(R^(8b))S(O)₂N(R^(8b)) group,        -   with the proviso that a 3- to 7-membered cycloalkyl,            cycloalkyleneimino, cycloalkyl-C₁₋₅-alkyl or            cycloalkyleneimino-C₁₋₃-alkyl group as hereinbefore defined            wherein two heteroatoms from the group comprising oxygen and            nitrogen are separated from one another by precisely one            optionally substituted —CH₂ group, is excluded,        -   while a 3- to 7-membered cycloalkyl, cycloalkyleneimino,            cycloalkyl-C₁₋₅-alkyl or cycloalkyleneimino-C₁₋₃-alkyl group            as hereinbefore defined may be substituted at one or two            —CH₂ groups by one or two C₁₋₃-alkyl groups in each case,    -   with the proviso that R⁴ and R⁵ cannot simultaneously be defined        as hydroxy or OR⁹ groups,-   R⁹ denotes a straight-chain or branched C₁₋₆-alkyl group,    -   while the hydrogen atoms of the straight-chain or branched        C₁₋₆-alkyl group may optionally be wholly or partly replaced by        fluorine atoms, and which may optionally be substituted by a        C₃₋₅-cycloalkyl group, a hydroxy, a C₁₋₅-alkyloxy group, while        the hydrogen atoms of the C₁₋₅-alkyloxy group may optionally be        wholly or partly replaced by fluorine atoms, an allyloxy,        propargyloxy, benzyloxy, C₁₋₅-alkylcarbonyloxy,        C₁₋₅-alkyloxycarbonyloxy, carboxy-C₁₋₅-alkyloxy,        C₁₋₅-alkyloxycarbonyl-C₁₋₅-alkyloxy, carboxy,        C₁₋₅-alkyloxycarbonyl, aminocarbonyl, C₁₋₅-alkylaminocarbonyl,        di-(C₁₋₅-alkyl)-aminocarbonyl, C₃₋₆-cycloalkyleneiminocarbonyl,        amino, C₁₋₅-alkylamino, di-(C₁₋₅-alkyl)-amino,        C₁₋₅-alkylcarbonylamino, C₁₋₅-alkylsulphonylamino,        N-(C₁₋₅-alkylsulphonyl)-C₁₋₅-alkylamino or        C₃₋₆-cycloalkylcarbonylamino group,        -   while the 6- to 7-membered cyclic groups of the            C₃₋₆-cycloalkyleneiminocarbonyl group in the cyclic moiety a            methylene group in the 4 position of a 6- or 7-membered            cycloalkyleneimino group by an oxygen or sulphur atom may be            replaced by a carbonyl, sulphinyl, sulphonyl or —NR^(8c)            group and additionally a methylene group adjacent to an            above-mentioned —NR^(8c) group may be replaced by a carbonyl            group,        -   with the proviso that the replacement of hydrogen atoms of            the first carbon atom of the straight-chain or branched            C₁₋₆-alkyl group by substituents from the group comprising            oxygen, sulphur or nitrogen is excluded,        -   a phenyl or heteroaryl group            -   which may optionally be mono- to trisubstituted in the                phenyl or heteroaryl moiety by identical or different                substituents selected from among halogen atoms,                C₁₋₅-alkyl, di-(C₁₋₅-alkyl)-amino, hydroxy,                C₁₋₅-alkyloxy, mono-, di- or trifluoromethoxy, carboxy-                and C₁₋₅-alkyloxycarbonyl groups,        -   a phenyl-C₁₋₅-alkyl or heteroaryl-C₁₋₅-alkyl group,            -   which may optionally be mono- to trisubstituted in the                phenyl or heteroaryl moiety by identical or different                substituents selected from among halogen atoms,                C₁₋₅-alkyl, di-(C₁₋₅-alkyl)-amino, hydroxy,                C₁₋₅-alkyloxy, mono-, di- or trifluoromethoxy, carboxy-                and C₁₋₅-alkyloxycarbonyl groups, and which may                optionally be substituted in the C₁₋₅-alkyl-moiety by a                hydroxy, a C₁₋₅-alkyloxy group, while the hydrogen atoms                of the C₁₋₅-alkyloxy group may optionally be wholly or                partly replaced by fluorine atoms, an allyloxy,                propargyloxy, benzyloxy, C₁₋₅-alkylcarbonyloxy,                C₁₋₅-alkyloxycarbonyloxy, carboxy-C₁₋₅-alkyloxy, or a                C₁₋₅-alkyloxycarbonyl-C₁₋₅-alkyloxy group;    -   a 3- to 7-membered cycloalkyl, cycloalkyl-C₁₋₅-alkyl or        cycloalkyleneimino-C₂₋₃-alkyl group,        -   wherein in 4- to 7-membered cyclic groups in the cyclic            moiety a methylene group may optionally be replaced by an            —N(R^(8c)) group, an oxygen or sulphur atom or a —S(O) or            —S(O)₂ group, or        -   wherein in 4- to 7-membered cyclic groups in the cyclic            moiety two adjacent methylene groups together may optionally            be replaced by a —C(O)N(R^(8b)) or —S(O)₂N(R^(8b)) group, or        -   wherein in 6- to 7-membered cyclic groups in the cyclic            moiety three adjacent methylene groups together may            optionally be replaced by a substituted —OC(O)N(R^(8b)) or            —N(R^(8b))C(O)N(R^(8b)) or —N(R^(8b))S(O)₂N(R^(8b)) group,            -   with the proviso that a 3- to 7-membered cycloalkyl,                cycloalkyl-C₁₋₅-alkyl or cycloalkyleneimino-C₂₋₃-alkyl                group as hereinbefore defined wherein two heteroatoms                from the group comprising oxygen and nitrogen are                separated from one another by precisely one optionally                substituted —CH₂ group, is excluded,            -   while a 3- to 7-membered cycloalkyl,                cycloalkyl-C₁₋₅-alkyl or cycloalkyleneimino-C₂₋₃-alkyl                group as hereinbefore defined may be substituted at one                or two —CH₂ groups by one or two C₁₋₃-alkyl groups in                each case,

B denotes a group of general formula

-   Y denotes a nitrogen atom or a CH group,-   R⁶ denotes a hydrogen, a halogen atom, an ethynyl, a methyl group, a    methoxy group, while the hydrogen atoms of the methoxy group may    optionally be wholly or partly replaced by fluorine atoms,    while, unless otherwise stated, by the term “heteroaryl group”    mentioned hereinbefore in the definitions is meant a monocyclic 5-    or 6-membered heteroaryl group, while    -   the 6-membered heteroaryl group contains one, two or three        nitrogen atoms and    -   the 5-membered heteroaryl group contains an imino group        optionally substituted by a C₁₋₃-alkyl, phenyl or        phenyl-C₁₋₃-alkyl group, an oxygen or sulphur atom or    -   an imino group optionally substituted by a C₁₋₃-alkyl, phenyl,        amino-C₂₋₃-alkyl, C₁₋₃-alkylamino-C₂₋₃-alkyl,        di-(C₁₋₃-alkyl)-amino-C₂₋₃-alkyl, a        C₃₋₆-cycloalkyleneimino-C₁₋₃-alkyl or phenyl-C₁₋₃-alkyl group or        an oxygen or sulphur atom and additionally a nitrogen atom or    -   an imino group optionally substituted by a C₁₋₃-alkyl or        phenyl-C₁₋₃-alkyl group and two or three nitrogen atoms,    -   and moreover a phenyl ring optionally substituted by a fluorine,        chlorine or bromine atom, a C₁₋₃-alkyl, hydroxy, C₁₋₃-alkyloxy        group, amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino or        C₃₋₆-cycloalkyleneimino group may be fused to the        above-mentioned monocyclic heteroaryl groups via two adjacent        carbon atoms    -   and the bond is effected via a nitrogen atom or a carbon atom of        the heterocyclic moiety or a fused-on phenyl ring,        while, unless otherwise stated, by the term “halogen atom”        mentioned hereinbefore in the definitions is meant an atom        selected from among fluorine, chlorine, bromine and iodine,        while the alkyl, alkenyl, alkynyl and alkoxy groups contained in        the above-mentioned definitions which have more than two carbon        atoms, unless otherwise stated, may be straight-chain or        branched and the alkyl groups in the previously mentioned        dialkylated groups, for example the dialkylamino groups, may be        identical or different,        and the hydrogen atoms of the methyl or ethyl groups contained        in the foregoing definitions, unless otherwise stated, may be        wholly or partly replaced by fluorine atoms,        the tautomers, the enantiomers, the diastereomers, the mixtures        thereof and the salts thereof.

A fourth embodiment of the present invention includes those compounds ofgeneral formula I, wherein

A denotes a group of general formula

wherein

-   m is the number 1 or 2,-   R^(8a) each independently of one another denote a hydrogen or    fluorine atom or a C₁₋₃-alkyl, hydroxy, hydroxy-C₁₋₃-alkyl,    C₁₋₃-alkoxy, C₁₋₃-alkoxy-C₁₋₃-alkyl, amino, C₁₋₃-alkylamino,    di-(C₁₋₃-alkyl)-amino, amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl,    or di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl group, while in the previously    mentioned substituted 5- to 7-membered groups A the heteroatoms F, O    or N optionally introduced with R^(8a) as substituents are not    separated by precisely one carbon atom from a heteroatom selected    from among N, O and S,-   R^(8b) each independently of one another denote a hydrogen atom or a    C₁₋₃-alkyl group,-   R^(8c) each independently of one another denote a hydrogen atom, a    C₁₋₃-alkyl, C₁₋₃-alkylcarbonyl, C₁₋₃-alkyloxycarbonyl or    C₁₋₃-alkylsulphonyl group,-   X¹ denotes a carbonyl, or sulphonyl group,-   X² denotes an oxygen atom or an —NR^(8b) group,-   X³ denotes a carbonyl, thiocarbonyl, C═NR^(8c), C═N—OR^(8c),    C═N—NO₂, C═N—CN or sulphonyl group,-   X⁴ denotes an oxygen or sulphur atom or an —NR^(8c) group,-   X⁵ denotes an oxygen atom or a —CH₂, —CHR^(8a) or —NR^(8c) group,-   R¹ denotes a hydrogen or halogen atom, a C₁₋₃-alkyl or C₁₋₃-alkoxy    group, while the hydrogen atoms of the C₁₋₃-alkyl or C₁₋₃-alkoxy    group may optionally be wholly or partly replaced by fluorine atoms,    a C₂₋₃-alkenyl, C₂₋₃-alkynyl, nitrile, nitro or amino group,-   R² denotes a hydrogen or fluorine atom or a methyl group,-   X denotes a nitrogen atom or a CH group,-   R³ denotes a hydrogen atom or a C₁₋₃-alkyl group,-   R⁴ denotes a hydrogen atom,    -   a straight-chain or branched C₁₋₄-alkyl group,        -   while the hydrogen atoms of the straight-chain or branched            C₁₋₄-alkyl group may optionally be wholly or partly replaced            by fluorine atoms, and which may optionally be substituted            by a C₁₋₃-alkyloxy group, while the hydrogen atoms of the            C₁₋₃-alkyloxy group may optionally be wholly or partly            replaced by fluorine atoms,-   R⁵ denotes a hydrogen atom, a hydroxy group, a OR⁹ group, a    C₂₋₄-alkenyl or C₂₋₄-alkynyl group,    -   a straight-chain or branched C₁₋₄-alkyl group,        -   while the hydrogen atoms of the straight-chain or branched            C₁₋₄-alkyl group may optionally be wholly or partly replaced            by fluorine atoms, and which may optionally be substituted            by a C₃₋₅-cycloalkyl group, a nitrile, hydroxy, a            C₁₋₅-alkyloxy group, while the hydrogen atoms of the            C₁₋₅-alkyloxy group may optionally be wholly or partly            replaced by fluorine atoms, an allyloxy, propargyloxy,            benzyloxy, C₁₋₅-alkylcarbonyloxy, C₁₋₅-alkyloxycarbonyloxy,            carboxy-C₁₋₅-alkyloxy, C₁₋₅-alkyloxycarbonyl-C₁₋₅-alkyloxy,            mercapto, C₁₋₅-alkylsulphanyl, C₁₋₅-alkylsulphonyl, carboxy,            C₁₋₅-alkyloxycarbonyl, aminocarbonyl,            C₁₋₅-alkylaminocarbonyl, di-(C₁₋₅-alkyl)-aminocarbonyl,            C₃₋₆-cycloalkyleneiminocarbonyl, aminosulphonyl,            C₁₋₅-alkylaminosulphonyl, di-(C₁₋₅-alkyl)-aminosulphonyl,            C₃₋₆-cycloalkyleneiminosulphonyl, amino, C₁₋₅-alkylamino,            di-(C₁₋₅-alkyl)-amino, C₁₋₅-alkylcarbonylamino,            C₁₋₅-alkylsulphonylamino,            N-(C₁₋₅-alkylsulphonyl)-C₁₋₅-alkylamino or            C₃₋₆-cycloalkylcarbonylamino group,            -   while the 6- to 7-membered cyclic groups of the                C₃₋₆-cycloalkyleneiminocarbonyl group in the cyclic                moiety a methylene group in the 4 position of a 6- or                7-membered cycloalkyleneimino group may be replaced by                an oxygen or sulphur atom, by a carbonyl, sulphinyl,                sulphonyl or —NR^(8c) group and additionally a methylene                group adjacent to an above-mentioned —NR^(8c) group may                be replaced by a carbonyl group,    -   a phenyl, heteroaryl, phenyl-C₁₋₅-alkyl or heteroaryl-C₁₋₅-alkyl        group, which may optionally be mono- to trisubstituted in the        phenyl or heteroaryl moiety may be substituted by identical or        different substituents selected from among halogen atoms,        C₁₋₅-alkyl, di-(C₁₋₅-alkyl)-amino, hydroxy, C₁₋₅-alkyloxy,        mono-, di- or trifluoromethoxy, carboxy- and        C₁₋₅-alkyloxycarbonyl groups,-   R⁹ denotes a straight-chain or branched C₁₋₄-alkyl group,    -   while the hydrogen atoms of the straight-chain or branched        C₁₋₄-alkyl group may optionally be wholly or partly replaced by        fluorine atoms, and which may optionally be substituted by a        C₃₋₅-cycloalkyl group, a hydroxy, a C₁₋₅-alkyloxy group, while        the hydrogen atoms of the C₁₋₅-alkyloxy group may optionally be        wholly or partly replaced by fluorine atoms, an allyloxy,        propargyloxy, benzyloxy, C₁₋₅-alkylcarbonyloxy,        C₁₋₅-alkyloxycarbonyloxy, carboxy-C₁₋₅-alkyloxy,        C₁₋₅-alkyloxycarbonyl-C₁₋₅-alkyloxy, carboxy,        C₁₋₅-alkyloxycarbonyl, aminocarbonyl, C₁₋₅-alkylaminocarbonyl,        di-(C₁₋₅-alkyl)-aminocarbonyl, C₃₋₆-cycloalkyleneiminocarbonyl,        amino, C₁₋₅-alkylamino, di-(C₁₋₅-alkyl)-amino,        C₁₋₅-alkylcarbonylamino, C₁₋₅-alkylsulphonylamino,        N-(C₁₋₅-alkylsulphonyl)-C₁₋₅-alkylamino or        C₃₋₆-cycloalkylcarbonylamino group,        -   while the 6- to 7-membered cyclic groups of the            C₃₋₆-cycloalkyleneiminocarbonyl group in the cyclic moiety a            methylene group in the 4 position of a 6- or 7-membered            cycloalkyleneimino group may be replaced by an oxygen or            sulphur atom, by a carbonyl, sulphinyl, sulphonyl or            —NR^(8c) group and additionally a methylene group adjacent            to an above-mentioned —NR^(8c) group may be replaced by a            carbonyl group,    -   with the proviso that the replacement of hydrogen atoms of the        first carbon atom of the straight-chain or branched C₁₋₄-alkyl        group by substituents from the group comprising oxygen, sulphur        or nitrogen is excluded,    -   a phenyl or heteroaryl group        -   which may optionally be mono- to trisubstituted in the            phenyl or heteroaryl moiety by identical or different            substituents selected from among halogen atoms, C₁₋₅-alkyl,            di-(C₁₋₅-alkyl)-amino, hydroxy, C₁₋₅-alkyloxy, mono-, di- or            trifluoromethoxy, carboxy- and C₁₋₅-alkyloxycarbonyl groups,    -   a phenyl-C₁ ₅-alkyl or heteroaryl-C₁₋₅-alkyl group,        -   which may optionally be mono- to trisubstituted in the            phenyl or heteroaryl moiety by identical or different            substituents selected from among halogen atoms, C₁₋₅-alkyl,            di-(C₁₋₅-alkyl)-amino, hydroxy, C₁₋₅-alkyloxy, mono-, di- or            trifluoromethoxy, carboxy- and C₁₋₅-alkyloxycarbonyl groups,            and which may optionally be substituted in the            C₁₋₅-alkyl-moiety by a hydroxy, a C₁₋₅-alkyloxy group, while            the hydrogen atoms of the C₁₋₅-alkyloxy group may optionally            be wholly or partly replaced by fluorine atoms, an allyloxy,            propargyloxy, benzyloxy, C₁₋₅-alkylcarbonyloxy,            C₁₋₅-alkyloxycarbonyloxy, carboxy-C₁₋₅-alkyloxy, or a            C₁₋₅-alkyloxycarbonyl-C₁₋₅-alkyloxy group;

B denotes a group of general formula

-   Y denotes a nitrogen atom or a CH group,-   R⁶ denotes a hydrogen, a halogen atom, an ethynyl, a methyl group, a    methoxy group, while the hydrogen atoms of the methoxy group may    optionally be wholly or partly replaced by fluorine atoms,    while, unless otherwise stated, by the term “heteroaryl group”    mentioned hereinbefore in the definitions is meant a monocyclic 5-    or 6-membered heteroaryl group, while    -   the 6-membered heteroaryl group contains one, two or three        nitrogen atoms and    -   the 5-membered heteroaryl group contains an imino group        optionally substituted by a C₁₋₃-alkyl, phenyl or        phenyl-C₁₋₃-alkyl group, or an oxygen or sulphur atom or    -   an imino group optionally substituted by a C₁₋₃-alkyl, phenyl,        amino-C₂₋₃-alkyl, C₁₋₃-alkylamino-C₂₋₃-alkyl,        di-(C₁₋₃-alkyl)-amino-C₂₋₃-alkyl, a        C₃₋₆-cycloalkyleneimino-C₁₋₃-alkyl or phenyl-C₁₋₃-alkyl group,        or an oxygen or sulphur atom and additionally a nitrogen atom or    -   an imino group optionally substituted by a C₁₋₃-alkyl or        phenyl-C₁₋₃-alkyl group and two or three nitrogen atoms,    -   and moreover a phenyl ring optionally substituted by a fluorine,        chlorine or bromine atom, a C₁₋₃-alkyl, hydroxy, C₁₋₃-alkyloxy        group, amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino or        C₃₋₆-cycloalkyleneimino group may be fused to the        above-mentioned monocyclic heteroaryl groups via two adjacent        carbon atoms    -   and the bond is effected via a nitrogen atom or a carbon atom of        the heterocyclic moiety or a fused-on phenyl ring,        while, unless otherwise stated, by the term “halogen atom”        mentioned hereinbefore in the definitions is meant an atom        selected from among fluorine, chlorine, bromine and iodine,        while the alkyl, alkenyl, alkynyl and alkoxy groups contained in        the above-mentioned definitions which have more than two carbon        atoms, unless otherwise stated, may be straight-chain or        branched and the alkyl groups in the previously mentioned        dialkylated groups, for example the dialkylamino groups, may be        identical or different,        and the hydrogen atoms of the methyl or ethyl groups contained        in the foregoing definitions, unless otherwise stated, may be        wholly or partly replaced by fluorine atoms,        the tautomers, the enantiomers, the diastereomers, the mixtures        thereof and the salts thereof.

A fifth embodiment of the present invention includes those compounds ofgeneral formula I, wherein

A denotes a group of general formula

wherein

-   m is the number 1 or 2,-   R^(8a) each independently of one another denote a hydrogen or    fluorine atom or a C₁₋₃-alkyl, hydroxy, hydroxy-C₁₋₃-alkyl,    C₁₋₃-alkoxy, C₁₋₃-alkoxy-C₁₋₃-alkyl, amino, C₁₋₃-alkylamino,    di-(C₁₋₃-alkyl)-amino, amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl,    or di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl group, while in the previously    mentioned substituted 5- to 7-membered groups A the heteroatoms F, O    or N optionally introduced with R^(8a) as substituents are not    separated by precisely one carbon atom from a heteroatom selected    from among N, O and S,-   R^(8b) each independently of one another denote a hydrogen atom or a    C₁₋₃-alkyl group,-   R^(8c) each independently of one another denote a hydrogen atom, a    C₁₋₃-alkyl, C₁₋₃-alkylcarbonyl, C₁₋₃-alkyloxycarbonyl or    C₁₋₃-alkylsulphonyl group,-   X¹ denotes a carbonyl or sulphonyl group,-   X² denotes an oxygen atom or an —NR^(8b) group,-   X³ denotes a carbonyl, thiocarbonyl, C═NR^(8c), C═N—OR^(8c),    C═N—NO₂, C═N—CN or sulphonyl group,-   X⁴ denotes an oxygen or sulphur atom or an —NR^(8c) group,-   R¹ denotes a hydrogen, fluorine, chlorine or bromine atom, a methyl    or methoxy group, while the hydrogen atoms of the methyl or methoxy    group may optionally be wholly or partly replaced by fluorine atoms,-   R² denotes a hydrogen or fluorine atom,-   X denotes a nitrogen atom or a CH group,-   R³ denotes a hydrogen atom or a C₁₋₃-alkyl group,-   R⁴ denotes a hydrogen atom,-   R⁵ denotes a hydrogen atom, a hydroxy group, a OR⁹ group, a    C₂₋₄-alkenyl or C₂₋₄-alkynyl group,    -   a straight-chain or branched C₁₋₄-alkyl group,        -   while the hydrogen atoms may optionally be wholly or partly            replaced by fluorine atoms, and which may optionally be            substituted by a hydroxy, a C₁₋₃-alkyloxy group, while the            hydrogen atoms of the C₁₋₃-alkyloxy group may be wholly or            partly replaced by fluorine atoms, a benzyloxy,            C₁₋₃-alkylcarbonyloxy, C₁₋₃-alkyloxycarbonyl, aminocarbonyl,            C₁₋₃-alkylaminocarbonyl, di-(C₁₋₃-alkyl)-aminocarbonyl,            C₃₋₆-cycloalkyleneiminocarbonyl, amino, C₁₋₃-alkylamino,            di-(C₁₋₃-alkyl)-amino, C₁₋₃-alkylcarbonylamino, or            C₁₋₃-alkylsulphonylamino group,    -   a phenyl, or C-linked heteroaryl group        -   while the heteroaryl group is selected from among pyrrolyl,            oxazolyl, imidazolyl, furanyl, thiophenyl, thiazolyl,            1,2,3-triazolyl, 1,2,4-triazolyl, tetrazolyl, pyridinyl,            pyrimidinyl and pyrazinyl, and which may optionally be mono-            to disubstituted in the heteroaryl moiety by identical or            different substituents selected from among halogen atoms,            C₁₋₃-alkyl, hydroxy, C₁₋₃-alkyloxy, mono-, di- and            trifluoromethoxy groups,        -   a phenyl-C₁₋₃-alkyl, heteroaryl-C₁₋₃-alkyl- group,        -   while the heteroaryl group is selected from among pyrrolyl,            oxazolyl, imidazolyl, furanyl, thiophenyl, thiazolyl,            1,2,3-triazolyl, 1,2,4-triazolyl, tetrazolyl, pyridinyl,            pyrimidinyl and pyrazinyl, and which may optionally be mono-            to disubstituted in the heteroaryl moiety by identical or            different substituents selected from among halogen atoms,            C₁₋₃-alkyl, hydroxy, C₁₋₃-alkyloxy, mono-, di- and            trifluoromethoxy groups, and which may optionally be            substituted in the C₁₋₃-alkyl moiety by a hydroxy, a            C₁₋₃-alkyloxy group, while the hydrogen atoms of the            C₁₋₃-alkyloxy group may optionally be wholly or partly            replaced by fluorine atoms, a C₁₋₅-alkylcarbonyloxy, or a            C₁₋₅-alkyloxycarbonyloxy group;

R⁹ denotes a straight-chain or branched C₁₋₄-alkyl group,

-   -   while the hydrogen atoms of the straight-chain or branched        C₁₋₄-alkyl group may optionally be wholly or partly replaced by        fluorine atoms, and which may optionally be substituted by a        hydroxy, a C₁₋₃-alkyloxy group, while the hydrogen atoms of the        C₁₋₃-alkyloxy group may optionally be wholly or partly replaced        by fluorine atoms, a benzyloxy, C₁₋₃-alkyloxycarbonyl,        aminocarbonyl, C₁₋₃-alkylaminocarbonyl,        di-(C₁₋₃-alkyl)-aminocarbonyl, C₃₋₆-cycloalkyleneiminocarbonyl,        amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino,        C₁₋₃-alkylcarbonylamino, C₁₋₃-alkyl-sulphonylamino group,        -   with the proviso that the replacement of hydrogen atoms of            the first carbon atom of the straight-chain or branched            C₁₋₄-alkyl group by substituents from the group comprising            oxygen, sulphur or nitrogen is excluded,    -   a phenyl, phenyl-C₁₋₂-alkyl, heteroaryl-C₁₋₂-alkyl or C-linked        heteroaryl group        -   while the heteroaryl group is selected from among pyrrolyl,            oxazolyl, imidazolyl, furanyl, thiophenyl, thiazolyl,            1,2,3-triazolyl, 1,2,4-triazolyl, tetrazolyl, pyridinyl,            pyrimidinyl and pyrazinyl, and which may optionally be mono-            to disubstituted in the heteroaryl moiety by identical or            different substituents selected from among halogen atoms,            C₁₋₃-alkyl, hydroxy, C₁₋₃-alkyloxy, mono-, di- and            trifluoromethoxy groups,

B denotes a group of general formula

-   R⁶ denotes a hydrogen, a chlorine or bromine atom, an ethynyl, a    methyl or a methoxy group,    while, unless otherwise stated, by the term “halogen atom” mentioned    hereinbefore in the definitions is meant an atom selected from among    fluorine, chlorine, bromine and iodine,    while the alkyl, alkenyl, alkynyl and alkoxy groups contained in the    above-mentioned definitions which have more than two carbon atoms,    unless otherwise stated, may be straight-chain or branched and the    alkyl groups in the previously mentioned dialkylated groups, for    example the dialkylamino groups, may be identical or different,    and the hydrogen atoms of the methyl or ethyl groups contained in    the foregoing definitions, unless otherwise stated, may be wholly or    partly replaced by fluorine atoms,    the tautomers, the enantiomers, the diastereomers, the mixtures    thereof and the salts thereof.

A sixth embodiment of the present invention includes those compounds ofgeneral formula I wherein

A denotes a group of general formula

wherein

-   m is the number 1 or 2,-   R^(8a) each independently of one another denote a hydrogen or    fluorine atom or a C₁₋₃-alkyl, hydroxy, hydroxy-C₁₋₃-alkyl,    C₁₋₃-alkoxy, C₁₋₃-alkoxy-C₁₋₃-alkyl, amino, C₁₋₃-alkylamino,    di-(C₁₋₃-alkyl)-amino, amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl,    or di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl group, while in the previously    mentioned substituted 5- to 7-membered groups A the heteroatoms F, O    or N optionally introduced with R^(8a) as substituents are not    separated by precisely one carbon atom from a heteroatom selected    from among N, O and S,-   R^(8b) each independently of one another denote a hydrogen atom or a    C₁₋₃-alkyl group,-   R^(8c) each independently of one another denote a hydrogen atom, a    C₁₋₃-alkyl, C₁₋₃-alkylcarbonyl, C₁₋₃-alkyloxycarbonyl or    C₁₋₃-alkylsulphonyl group,-   X¹ denotes a carbonyl or sulphonyl group,-   X² denotes an oxygen atom or an —NR^(8b) group,-   X³ denotes a carbonyl or sulphonyl group,-   X⁴ denotes an oxygen atom or an —NR^(8c) group,-   R¹ denotes a hydrogen, fluorine, chlorine or bromine atom, a methyl,    trifluoromethyl or methoxy group,-   R² denotes a hydrogen atom,-   X denotes a nitrogen atom or a CH group,-   R³ denotes a hydrogen atom or a methyl group,-   R⁴ denotes a hydrogen atom,-   R⁵ denotes a hydrogen atom, a hydroxy group, a OR⁹ group, an allyl    or methallyl group,    -   a methyl group which may optionally be substituted independently        of one another by a C₁₋₃-alkyl, hydroxy, OR⁹ group,        aminocarbonyl, pyridin-4-yl, pyridin-3-yl, pyridin-2-yl,        pyrazin-2-yl, pyrazin-3-yl or phenyl group,    -   a phenyl group,-   R⁹ a straight-chain or branched C₁₋₄-alkyl group,    -   which may optionally be substituted by a hydroxy, a C₁₋₃-alkoxy        group, a benzyloxy or a di-(C₁₋₃-alkyl)-amino group,        -   with the proviso that the replacement of hydrogen atoms of            the first carbon atom of the straight-chain or branched            C₁₋₄-alkyl group by substituents from the group comprising            oxygen or nitrogen is excluded,

B denotes a group of general formula

-   R⁶ denotes a chlorine or bromine atom or an ethynyl group,    while, unless otherwise stated, by the term “halogen atom” mentioned    hereinbefore in the definitions is meant an atom selected from among    fluorine, chlorine, bromine and iodine,    while the alkyl, alkenyl, alkynyl and alkoxy groups contained in the    above-mentioned definitions which have more than two carbon atoms,    unless otherwise stated, may be straight-chain or branched and the    alkyl groups in the previously mentioned dialkylated groups, for    example the dialkylamino groups, may be identical or different,    and the hydrogen atoms of the methyl or ethyl groups contained in    the foregoing definitions, unless otherwise stated, may be wholly or    partly replaced by fluorine atoms,    the tautomers, the enantiomers, the diastereomers, the mixtures    thereof and the salts thereof.

A seventh embodiment of the present invention includes those compoundsof general formula I, wherein the group B denotes the group

the tautomers, the enantiomers, the diastereomers, the mixtures thereofand the salts thereof.

An eighth embodiment of the present invention includes those compoundsof general formula I, wherein the group B denotes the group

the tautomers, the enantiomers, the diastereomers, the mixtures thereofand the salts thereof.

A ninth embodiment of the present invention includes those compounds ofgeneral formula I, wherein the group A denotes the group

the tautomers, the enantiomers, the diastereomers, the mixtures thereofand the salts thereof.

Within the scope of the present application, unless otherwise defined,the following general expressions used in the definitions are definedmore specifically as shown below or are represented by examples.

Examples of the monocyclic heteroaryl groups mentioned hereinbefore inthe definitions are the pyridyl, N-oxy-pyridyl, pyrazolyl, pyridazinyl,pyrimidinyl, pyrazinyl, [1,2,3]triazinyl, [1,3,5]triazinyl,[1,2,4]triazinyl, pyrrolyl, imidazolyl, [1,2,4]triazolyl,[1,2,3]triazolyl, tetrazolyl, furanyl, isoxazolyl, oxazolyl,[1,2,3]oxadiazolyl, [1,2,4]oxadiazolyl, furazanyl, thiophenyl,thiazolyl, isothiazolyl, [1,2,3]thiadiazolyl, [1,2,4]thiadiazolyl or[1,2,5]thiadiazolyl group.

Examples of the bicyclic heteroaryl groups mentioned hereinbefore in thedefinitions are the benzimidazolyl, benzofuranyl, benzo[c]furanyl,benzothiophenyl, benzo[c]thiophenyl, benzothiazolyl,benzo[c]isothiazolyl, benzo[d]isothiazolyl, benzooxazolyl,benzo[c]isoxazolyl, benzo[d]isoxazolyl, benzo[1,2,5]oxadiazolyl,benzo[1,2,5]thiadiazolyl, benzo[1,2,3]thiadiazolyl,benzo[d][1,2,3]triazinyl, benzo[1,2,4]triazinyl, benzotriazolyl,cinnolinyl, quinolinyl, N-oxy-quinolinyl, isoquinolinyl, quinazolinyl,N-oxy-quinazolinyl, quinoxalinyl, phthalazinyl, indolyl, isoindolyl or1-oxa-2,3-diaza-indenyl group.

Examples of the C₁₋₆-alkyl groups mentioned hereinbefore in thedefinitions are the methyl, ethyl, 1-propyl, 2-propyl, n-butyl,sec-butyl, tert-butyl, 1-pentyl, 2-pentyl, 3-pentyl, neo-pentyl,3-methyl-2-butyl, 1-hexyl, 2-hexyl, 3-hexyl, 3-methyl-2-pentyl,4-methyl-2-pentyl, 3-methyl-3-pentyl, 2-methyl-3-pentyl,2,2-dimethyl-3-butyl or 2,3-dimethyl-2-butyl group.

Examples of the C₁₋₅-alkyloxy groups mentioned hereinbefore in thedefinitions are the methyloxy, ethyloxy, 1-propyloxy, 2-propyloxy,n-butyloxy, sec-butyloxy, tert-butyloxy, 1-pentyloxy, 2-pentyloxy,3-pentyloxy or neo-pentyloxy group.

Examples of the C₂₋₆-alkenyl groups mentioned hereinbefore in thedefinitions are the ethenyl, 1-propen-1-yl, 2-propen-1-yl, 1-buten-1-yl,2-buten-1-yl, 3-buten-1-yl, 1-penten-1-yl, 2-penten-1-yl, 3-penten-1-yl,4-penten-1-yl, 1-hexen-1-yl, 2-hexen-1-yl, 3-hexen-1-yl, 4-hexen-1-yl,5-hexen-1-yl, but-1-en-2-yl, but-2-en-2-yl, but-1-en-3-yl,2-methyl-prop-2-en-1-yl, pent-1-en-2-yl, pent-2-en-2-yl, pent-3-en-2-yl,pent-4-en-2-yl, pent-1-en-3-yl, pent-2-en-3-yl, 2-methyl-but-1-en-1-yl,2-methyl-but-2-en-1-yl, 2-methyl-but-3-en-1-yl, 2-ethyl-prop-2-en-1-yl,hex-1-en-2-yl, hex-2-en-2-yl, hex-3-en-2-yl, hex-4-en-2-yl,hex-5-en-2-yl, hex-1-en-3-yl, hex-2-en-3-yl, hex-3-en-3-yl,hex-4-en-3-yl, hex-5-en-3-yl, hex-1-en-4-yl, hex-2-en-4-yl,hex-3-en-4-yl, hex-4-en-4-yl, hex-5-en-4-yl, 4-methyl-pent-1-en-3-yl,3-methyl-pent-1-en-3-yl, 2-methyl-pent-1-en-3-yl, 2 ,3-dimethyl-but-1-en-3-yl, 3,3-dimethyl-but-1-en-2-yl or2-ethyl-but-1-en-3-yl group,

Examples of the C₂₋₆-alkynyl groups mentioned hereinbefore in thedefinitions are the ethynyl, 1-propynyl, 2-propynyl, 1-butyn-1-yl,1-butyn-3-yl, 2-butyn-1-yl, 3-butyn-1-yl, 1-pentyn-1-yl, 1-pentyn-3-yl,1-pentyn-4-yl, 2-pentyn-1-yl, 2-pentyn-3-yl, 3-pentyn-1-yl,4-pentyn-1-yl, 2-methyl-1-butyn-4-yl, 3-methyl-1-butyn-1-yl,3-methyl-1-butyn-3-yl, 1-hexyn-1-yl, 2-hexyn-1-yl, 3-hexyn-1-yl,4-hexyn-1-yl, 5-hexyn-1-yl, 1-hexyn-3-yl, 1-hexyn-4-yl, 1-hexyn-5-yl,2-hexyn-4-yl, 2-hexyn-5-yl, 3-hexyn-5-yl, 3-methyl-1-pentyn-3-yl,4-methyl-1-pentyn-3-yl, 3-methyl-1-pentyn-4-yl, 4-methyl-1-pentyn-4-yl,4-methyl-2-pentyn-4-yl, 4-methyl-2-pentyn-1-yl,2,2-dimethyl-3-butyn-1-yl or 2-ethyl-3-butyn-1-yl group.

By a group which can be converted in vivo into a carboxy group is meantfor example a carboxy group esterified with an alcohol wherein thealcoholic moiety is preferably a C₁₋₆-alkanol, a phenyl-C₁₋₃-alkanol, aC₃₋₉-cycloalkanol, a C₅₋₇-cycloalkenol, a C₃₋₅-alkenol, aphenyl-C₃₋₅-alkenol, a C₃₋₅-alkynol or phenyl-C₃₋₅-alkynol with theproviso that no bond to the oxygen atom starts from a carbon atom thatcarries a double or triple bond, a C₃₋₈-cycloalkyl-C₁₋₃-alkanol or analcohol of formulaR¹⁰—CO—O—(R¹¹CR¹²)—OH,wherein

-   -   R¹⁰ denotes a C₁₋₈-alkyl, C₅₋₇-cycloalkyl, phenyl or        phenyl-C₁₋₃-alkyl group,    -   R¹¹ denotes a hydrogen atom, a C₁₋₃-alkyl, C₅₋₇-cycloalkyl or        phenyl group and    -   R¹² denotes a hydrogen atom or a C₁₋₃-alkyl group.

Preferred groups which may be cleaved from a carboxy group in vivoinclude a C₁₋₆-alkoxy group such as the methoxy, ethoxy, n-propyloxy,isopropyloxy, n-butyloxy, n-pentyloxy, n-hexyloxy or cyclohexyloxy groupor a phenyl-C₁₋₃-alkoxy group such as the benzyloxy group.

By a group which may be converted in vivo into a hydroxyl group is meantfor example a hydroxyl group esterified with a carboxylic acid whereinthe carboxylic acid moiety is preferably a C₁₋₇-alkanoic acid, aphenyl-C₁₋₃-alkanoic acid, a C₃₋₉-cycloalkylcarboxylic acid, aC₅₋₇-cycloalkenecarboxylic acid, a C₃₋₇-alkenoic acid, aphenyl-C₃₋₅-alkenoic acid, a C₃₋₇-alkynoic acid or phenyl-C₃₋₅-alkynoicacid, while individual methylene groups of the carboxylic acid group maybe replaced by oxygen atoms, with the proviso that no bond to the oxygenatom starts from a carbon atom which carries a double or triple bond.

Preferred groups which may be cleaved from a hydroxyl group in vivoinclude a C₁₋₇-acyl group such as the formyl, acetyl, n-propionyl,isopropionyl, n-propanoyl, n-butanoyl, n-pentanoyl, n-hexanoyl orcyclohexylcarbonyl group or a benzoyl group as well as a methoxyacetyl,1-methoxypropionyl, 2-methoxypropionyl or 2-methoxy-ethoxyacetyl group.

Those compounds of general formula I wherein A, R⁴ and/or R⁵ contains agroup which can be converted in vivo into a carboxy or hydroxyl groupare prodrugs for those compounds of general formula I wherein A, R⁴and/or R⁵ contains a carboxy or hydroxyl group.

The following preferred compounds of general formula I will now bementioned by way of example:

-   (1) 5-bromo-thiophene-2-carboxylic    acid-{1-[3-chloro-4-(2-oxo-[1,3]oxazinan-3-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (2) (R)-5-bromo-thiophene-2-carboxylic    acid-{1-[2-fluoro-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (3) 5-chloro-thiophene-2-carboxylic    acid-{1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (4) 5-bromo-thiophene-2-carboxylic    acid-{1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (5) 5-chloro-pyridine-2-carboxylic    acid-{1-[3-methyl-4-(3-oxo-morpholi    n-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (6) 5-methyl-thiophene-2-carboxylic    acid-{1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (7) 5-bromo-thiazole-2-carboxylic    acid-{1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (8) 5-chloro-thiophene-2-carboxylic    acid-{1-[3-chloro-4-(2-oxo-[1,3]oxazinan-3-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (9) (R)-5-bromo-thiophene-2-carboxylic    acid-{1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (10) (R)-5-bromo-thiophene-2-carboxylic    acid-{5-oxo-1-[5-(3-oxo-morpholin-4-yl)-pyridin-2-yl]-pyrrolidin-3-yl}-amide-   (11) (S)-5-bromo-thiophene-2-carboxylic    acid-{1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (12) (R)-5-chloro-thiophene-2-carboxylic    acid-{1-[2-fluoro-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (13) 5-bromo-thiophene-2-carboxylic    acid-{1-[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (14) 5-chloro-thiophene-2-carboxylic    acid-{1-[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (15) 2-bromo-thiazole-5-carboxylic    acid-{1-[3-chloro-4-(2-oxo-[1,3]-oxazinan-3-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (16) 5-bromo-thiophene-2-carboxylic    acid-{(3R,4R)-4-methyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (17) (R)-5-bromo-thiophene-2-carboxylic    acid-{1-[2.5-difluoro-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (18) 5-bromo-thiophene-2-carboxylic    acid-{1-[3-methyl-4-(5-oxo-[1,4]oxazepan-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (19) (R)-5-ethynyl-thiophene-2-carboxylic    acid-{1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (20) 5-ethynyl-thiophene-2-carboxylic    acid-{1-[3-methyl-4-(5-oxo-[1,4]oxazepan-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (21) 5-bromo-thiophene-2-carboxylic    acid-{1-[3-methyl-4-(2-oxo-[1,3]oxazepan-3-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (22) 5-ethynyl-thiophene-2-carboxylic    acid-{(3R,4R)-4-methyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (23) (R)-5-bromo-thiophene-2-carboxylic    acid-{1-[6-methyl-5-(3-oxo-morpholin-4-yl)-pyridin-2-yl]-5-oxo-pyrrolidin-3-yl}-amide-   (24) (R)-5-bromo-thiophene-2-carboxylic    acid-{1-[4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (25) (R)-5-ethynyl-thiophene-2-carboxylic    acid-{5-oxo-1-[6-methyl-5-(3-oxo-morpholin-4-yl)-pyridin-2-yl]-pyrrolidin-3-yl}-amide-   (26) (R)-5-chloro-thiophene-2-carboxylic    acid-{1-[6-methyl-5-(3-oxo-morpholin-4-yl)-pyridin-2-yl]-5-oxo-pyrrolidin-3-yl}-amide-   (27) (R)-5-ethynyl-thiophene-2-carboxylic    acid-{5-oxo-1-[4-(3-oxo-morpholin-4-yl)-phenyl]-pyrrolidin-3-yl}-amide-   (28) (R)-5-chloro-thiophene-2-carboxylic    acid-{5-oxo-1-[4-(3-oxo-morpholin-4-yl)-phenyl]-pyrrolidin-3-yl}-amide-   (29) (R)-4-bromo-thiophene-2-carboxylic    acid-{1-[5-oxo-4-(3-oxo-morpholin-4-yl)-phenyl]-pyrrolidin-3-yl}-amide-   (30) (R)-5-bromo-thiophene-2-carboxylic    acid-{5-oxo-1-[4-(2-oxo-piperidin-1-yl)-phenyl]-pyrrolidin-3-yl}-amide-   (31) (R)-5-ethynyl-thiophene-2-carboxyl ic    acid-{5-oxo-1-[4-(2-oxo-piperidi    n-1-yl)-phenyl]-pyrrolidin-3-yl}-amide-   (32) (R)-5-ethynyl-thiophene-2-carboxylic    acid-{5-oxo-1-[4-(3-oxo-morpholin-4-yl)-3-trifluoromethyl-phenyl]-pyrrolidin-3-yl}-amide-   (33) (R)-5-bromo-thiophene-2-carboxylic    acid-{5-oxo-1-[4-(3-oxo-morpholin-4-yl)-3-trifluoromethyl-phenyl]-pyrrolidin-3-yl}-amide-   (34) (R)-5-chloro-thiophene-2-carboxylic    acid-{5-oxo-1-[4-(3-oxo-morpholin-4-yl)-3-trifluoromethyl-phenyl]-pyrrolidin-3-yl}-amide-   (35) (R)-5-chloro-thiophene-2-carboxylic    acid-{1-[4-(1,1-dioxo-1□⁶-[1,2]thiazinan-2-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (36) (R)-5-bromo-thiophene-2-carboxylic    acid-{1-[4-(1,1-dioxo-1□⁶-[1,2]thiazinan-2-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (37) (R)-5-ethynyl-thiophene-2-carboxylic    acid-{1-[4-(1,1-dioxo-1□⁶-[1,2]thiazinan-2-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (38) (R)-5-bromo-thiophene-2-carboxylic    acid-{1-[3-chloro-4-(2-oxo-tetrahydro-pyrimidin-1-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (39) (R)-4-bromo-thiophene-2-carboxylic    acid-{1-[4-(1,1-dioxo-1□⁶-[1,2,6]thiadiazinan-2-yl)-3-methyl-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (40) (R)-4-bromo-thiophene-2-carboxylic    acid-{1-[3-methyl-4-(3-oxo-[1,4]oxazepan-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (41) 5-bromo-thiophene-2-carboxylic    acid-{1-[3-chloro-4-(4-methyl-[1,4]diazepam-1-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (42) 5-chloro-thiophene-2-carboxylic    acid-[1-(4-azepan-1-yl-3-chloro-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (43) 5-ethynyl-thiophene-2-carboxylic    acid-{1-[3-methyl-4-(5-oxo-[1,4]oxazepan-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (44) 5-ethynyl-thiophene-2-carboxyl ic    acid-{1-[3-chloro-4-(2-oxo-azepan-1-yl    )-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (45) 5-chloro-thiophene-2-carboxylic    acid-{1-[3-chloro-4-(2-oxo-azepan-1-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (46) 5-bromo-thiophene-2-carboxylic    acid-{(3R,4S)-4-hydroxy-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (47) (R)-5-bromo-thiophene-2-carboxylic    acid-{1-[3-chloro-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide,-   (48) (R)-5-bromo-furan-2-carboxylic    acid-{1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide,-   (49) (R)-5-chloro-thiophene-2-carboxylic    acid-{1-[3-chloro-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide,-   (50) (R)-5-bromo-thiophene-2-carboxylic    acid-{1-[3-bromo-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide,-   (51) (R)-5-bromo-thiophene-2-carboxylic    acid-{1-[3-fluoro-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide,-   (52) (R)-5-chloro-1H-indole-6-carboxylic    acid-{1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide,-   (53) (R)-5-bromo-thiophene-2-carboxylic    acid-{1-[2-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide,-   (54) (R)-5-chloro-naphthalene-2-carboxylic    acid-{1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide,-   (55) (R)-5-bromo-thiophene-2-carboxylic    acid-{1-[4-(3-oxo-morpholin-4-yl)-3-trifluoromethoxy-phenyl]-5-oxo-pyrrolidin-3-yl}-amide,-   (56) (R)-5-chloro-1H-indole-2-carboxylic    acid-{1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide,-   (57) (R)-5-bromo-thiophene-2-carboxylic    acid-{1-[3-methoxy-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide,-   (58) (R)-5-chloro-benzo[b]thiophene-2-carboxylic    acid-{1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide,-   (59) (R)-5-bromo-thiophene-2-carboxylic    acid-{1-[3-nitro-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide,-   (60) (R)-5-bromo-thiophene-2-carboxylic    acid-{1-[3-amino-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide,-   (61) (R)-5-chloro-1H-benzimidazole-2-carboxylic    acid-{1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide,-   (62) 5-bromo-thiophene-2-carboxylic    acid-{4-methoxy-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide,-   (63) 5-ethynyl-thiophene-2-carboxylic    acid-{4-methoxy-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide,-   (64) 5-bromo-thiophene-2-carboxylic    acid-{4-methoxy-1-[3-chloro-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide,-   (65) 5-bromo-thiophene-2-carboxylic    acid-{4-methoxy-1-[4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide,-   (66) 5-bromo-thiophene-2-carboxylic    acid-{4-benzyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (67) 5-bromo-thiophene-2-carboxylic    acid-{1-[3-chloro-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-4-pyridin-4-ylmethyl-pyrrolidin-3-yl}-amide-   (68) 5-bromo-thiophene-2-carboxylic    acid-{1-[3-chloro-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-4-pyridin-3-ylmethyl-pyrrolidin-3-yl}-amide-   (69) 5-bromo-thiophene-2-carboxylic    acid-{1-[3-chloro-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-4-pyridin-2-ylmethyl-pyrrolidin-3-yl}-amide-   (70) 5-bromo-thiophene-2-carboxylic    acid-{1-[3-chloro-4-(3-oxo-morpholin-4-yl)-phenyl]-4-methyl-5-oxo-pyrrolidin-3-yl}-amide-   (71) 5-bromo-thiophene-2-carboxylic    acid-{4-isobutyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (72) 5-bromo-thiophene-2-carboxylic    acid-{4-carbamoylmethyl-5-oxo-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-pyrrolidin-3-yl}-amide-   (73) 5-bromo-thiophene-2-carboxylic    acid-{4-methyl-5-oxo-1-[4-(3-oxo-morpholin-4-yl)-phenyl]-pyrrolidin-3-yl}-amide-   (74) 5-bromo-thiophene-2-carboxylic    acid-{4-methyl-1-[6-methyl-5-(3-oxo-morpholin-4-yl)-pyridin-2-yl]-5-oxo-pyrrolidin-3-yl}-amide-   (75) 5-bromo-thiophene-2-carboxylic    acid-{5-oxo-1-[4-(3-oxo-morpholin-4-yl)-3-trifluoromethoxy-phenyl]-4-prop-2-ynyl-pyrrolidin-3-yl}-amide-   (76) 5-bromo-thiophene-2-carboxylic    acid-{4-allyl-1-[3-chloro-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (77) 5-bromo-thiophene-2-carboxylic    acid-{5-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-4-oxo-5-aza-spiro[2.4]hept-7-yl}-amide-   (78) 5-ethynyl-thiophene-2-carboxylic    acid-{3-methyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide,-   (79) 5-bromo-thiophene-2-carboxylic    acid-{3-methyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide,-   (80) 5-bromo-thiophene-2-carboxylic    acid-{3,4-dimethyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide,-   (81) 5-bromo-thiophene-2-carboxylic    acid-{3-propyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide,-   (82) 5-bromo-thiophene-2-carboxylic    acid-{3-methyl-5-oxo-1-[4-(3-oxo-morpholin-4-yl)-phenyl]-pyrrolidin-3-yl}-amide,-   (83) 5-ethynyl-thiophene-2-carboxylic    acid-{3-methyl-5-oxo-1-[5-(3-oxo-morpholin-4-yl)-pyridin-2-yl]-pyrrolidin-3-yl}-amide,-   (84) 5-ethynyl-thiophene-2-carboxylic    acid-{3-methyl-1-[6-methyl-5-(3-oxo-morpholin-4-yl)-pyridin-2-yl]-5-oxo-pyrrolidin-3-yl}-amide,-   (85) 5-bromo-thiophene-2-carboxylic    acid-{4-dimethylaminocarbamoylmethyl-3-methyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide,-   (86) (R)-5-bromo-thiophene-2-carboxylic    acid-{1-[3-chloro-4-(5-oxo-[1,4]oxazepan-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (87) (R)-5-chloro-thiophene-2-carboxylic    acid-{1-[3-methyl-4-(5-oxo-[1,4]oxazepan-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (88) (R)-5-bromo-thiophene-2-carboxylic    acid-{1-[6-methyl-5-(5-oxo-[1,4]oxazepan-4-yl)-pyridin-2-yl]-5-oxo-pyrrolidin-3-yl}-amide-   (89) (R)-5-ethynyl-thiophene-2-carboxylic    acid-{1-[6-methyl-5-(5-oxo-[1,4]oxazepan-4-yl)-pyridin-2-yl]-5-oxo-pyrrolidin-3-yl}-amide-   (90) (R)-5-bromo-thiophene-2-carboxylic    acid-{5-oxo-1-[4-(5-oxo-[1,4]oxazepan-4-yl)-phenyl]-pyrrolidin-3-yl}-amide-   (91) (R)-5-bromo-thiophene-2-carboxylic    acid-{4-methyl-1-[3-methyl-4-(5-oxo-[1,4]oxazepan-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (92) (R)-5-bromo-thiophene-2-carboxylic    acid-{4-methoxy-1-[3-methyl-4-(5-oxo-[1,4]oxazepan-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (93) (R)-5-bromo-thiophene-2-carboxylic    acid-{4-hydroxy-1-[3-methyl-4-(5-oxo-[1,4]oxazepan-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (94) 5-bromo-thiophene-2-carboxylic    acid-{4-ethoxy-1-[3-methyl-4-(5-oxo-[1,4]oxazepan-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (95) 5-bromo-thiophene-2-carboxylic    acid-{3-methyl-5-oxo-1-[4-(5-oxo-[1,4]oxazepan-4-yl)-phenyl]-pyrrolidin-3-yl}-amide-   (96) 5-bromo-thiophene-2-carboxylic    acid-{3-methyl-1-[3-methyl-4-(5-oxo-[1,4]oxazepan-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (97) 5-ethynyl-thiophene-2-carboxylic    acid-{3-methyl-1-[3-methyl-4-(5-oxo-[1,4]oxazepan-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (98) 5-ethynyl-thiophene-2-carboxylic    acid-{4-methoxy-1-[3-methyl-4-(5-oxo-[1,4]oxazepan-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (99) 5-bromo-thiophene-2-carboxylic    acid-{4-(2-methoxy-ethoxy)-1-[3-methyl-4-(5-oxo-[1,4]oxazepan-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (100) 5-ethynyl-thiophene-2-carboxylic    acid-{1-[3-methyl-4-(2-oxo-tetrahydropyrimidin-1-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (101) (R)-5-bromo-thiophene-2-carboxylic    acid-{1-[4-(1,1-dioxo-1□⁶-[1,2]thiazinan-2-yl)-3-methyl-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (102) 5-bromo-thiophene-2-carboxylic    acid-{1-[4-(1-dioxo-1□⁶-[1,2,6]thiadiazinan-2-yl)-3-methyl-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (103) (R)-5-bromo-thiophene-2-carboxylic    acid-{1-[3-methyl-4-(4-methyl-2-oxo-piperazin-1-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (104) (R)-5-bromo-thiophene-2-carboxylic    acid-{1-[3-chloro-4-(2-oxo-pyrrolidin-1-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (105) 5-bromo-thiophene-2-carboxylic    acid-{1-[3-bromo-4-(4-methyl-2-oxo-oxazolidin-3-yl)-phenyl]-4-methyl-5-oxo-pyrrolidin-3-yl}-amide-   (106) (R)-5-bromo-thiophene-2-carboxylic    acid-{1-[4-(1,1-dioxo-1□⁶-isothiazolidin-2-yl)-3-methyl-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (107) 5-bromo-thiophene-2-carboxylic    acid-{1-[4-(1,1-dioxo-1□⁶-[1,2,5]thiadiazolidin-2-yl)-3-methoxy-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (108) 5-bromo-thiophene-2-carboxylic    acid-{1-[4-(3-methyl-2-oxo-tetrahydropyrimidin-1-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (109) 5-bromo-thiophene-2-carboxylic    acid-{1-[3-methyl-4-(3-oxo-thiomorpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (110) 5-bromo-thiophene-2-carboxylic    acid-{1-[3-methyl-4-(3-methyl-5-oxo-thiomorpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (111) (R)-5-bromo-thiophene-2-carboxylic    acid-{1-[4-(1,1-dioxo-1□⁶-[1,2]thiazepan-2-yl)-3-methyl-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (112) 5-bromo-thiophene-2-carboxylic    acid-{3,4-dimethyl-1-[3-methyl-4-(2-oxo-azepan-1-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (113) 5-bromo-thiophene-2-carboxylic    acid-{1-[3-chloro-4-(2-oxo-[1,3]oxazepan-3-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (114) 5-bromo-thiophene-2-carboxylic    acid-{1-[3-methyl-4-(4-methyl-7-oxo-[1,4]diazepan-1-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (115) 5-bromo-thiophene-2-carboxylic    acid-{1-[3-chloro-4-(2-methyl-2-oxo-pyrrolidin-1-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (116) 5-bromo-thiophene-2-carboxylic    acid-{1-[3-chloro-4-(2-methyl-2-oxo-pyrrolidin-1-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (117) 5-bromo-thiophene-2-carboxylic    acid-{1-[4-(2-dimethylaminomethyl-5-oxo-pyrrolidin-1-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (118) (R)-5-bromo-thiophene-2-carboxylic    acid-{1-[3-ethyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (119) 5-bromo-thiophene-2-carboxylic    acid-{1-[4-(2-imino-piperidin-1-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (120) 5-bromo-thiophene-2-carboxylic    acid-{1-[4-(2-methoxyimino-piperidin-1-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (121) 5-bromo-thiophene-2-carboxylic    acid-{1-[3-methyl-4-(3-thioxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (122) 5-bromo-thiophene-2-carboxylic    acid-{4-hydroxymethyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (123) 5-bromo-thiophene-2-carboxylic    acid-{4-methoxymethyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (124) 5-bromo-thiophene-2-carboxylic    acid-{4-(2-hydroxy-ethyl)-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (125) 5-bromo-thiophene-2-carboxylic    acid-{(3R,4R)-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-4-propyl-pyrrolidin-3-yl}-amide-   (126) 5-bromo-thiophene-2-carboxylic    acid-{(3R,4R)-4-methoxymethyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (127) 5-chloro-thiophene-2-carboxylic    acid-{(3R,4R)-4-benzyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (128) 5-ethynyl-thiophene-2-carboxylic    acid-{(3R,4R)-4-benzyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (129) 5-chloro-thiophene-2-carboxylic    acid-{(3R,4R)-4-methoxymethyl-5-oxo-1-[4-(3-oxo-morpholin-4-yl)-phenyl]-pyrrolidin-3-yl}-amide-   (130) 5-chloro-thiophene-2-carboxylic    acid-{(3R,4R)-4-allyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (131) 5-bromo-thiophene-2-carboxylic    acid-{(3R,4R)-4-allyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (132) 5-chloro-thiophene-2-carboxylic    acid-{(3R,4R)-4-methoxymethyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (133) 5-chloro-thiophene-2-carboxylic    acid-{3-methyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (134) (R)-5-chloro-thiophene-2-carboxylic    acid-{1-[3-fluoro-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (135) 5-chloro-thiophene-2-carboxylic    acid-(1-{3-chloro-4-[2-(2-diethylamino-ethyl)-piperidin-1-yl]-phenyl}-5-oxo-pyrrolidin-3-yl)-amide-   (136) 5-bromo-thiophene-2-carboxylic    acid-[1-(3-chloro-4-[1,4]diazepan-1-yl-phenyl)-5-oxo-pyrrolidin-3-yl]-amide-   (137) (R)-5-bromo-thiophene-2-carboxylic    acid-{1-[4-(1,1-dioxo-1□⁶-[1,2,6]thiadiazinan-2-yl)-3-methyl-phenyl]-5-oxo-pyrrolidin-3-yl}-amide-   (138) (R)-5-bromo-thiophene-2-carboxylic    acid-{1-[3-methyl-4-(3-oxo-[1,4]oxazepan-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide    the tautomers, the enantiomers, the diastereomers, the mixtures    thereof and the salts thereof, while the compounds

For example the following particularly preferred compounds of generalformula I may be mentioned:

(1), (2), (3), (4), (6), (8), (9), (10), (12), (16), (17), (18), (19),(20), (21), (22), (23), (24), (25), (26), (27), (28), (30), (31), (32),(33), (34), (35), (36), (37), (38), (39), (40), (41), (42), (43), (44),(45), (46), (47), (49), (57), (59), (60), (62), (63), (64), (65), (66),(67), (68), (69), (70), (71), (72), (74), (76), (78), (82), (84), (85),(86), (87), (90), (92), (93), (94), (98), (99), (103), (104), (108),(109), (112), (114), (117), (122), (123), (124), (125), (126), (127),(128), (129), (130), (131), (132), (134), (135), (136), (137), (138),

the tautomers, the enantiomers, the diastereomers, the mixtures and thesalts of which are particularly preferred.

For example the following most particularly preferred compounds ofgeneral formula I may be mentioned:

(1), (2), (3), (8), (9), (10), (16), (17), (18), (19), (20), (21), (22),(23), (24), (25), (26), (27), (28), (30), (31), (33), (40), (44), (45),(46), (62), (63), (64), (65), (68), (72), (73), (74), (85), (86), (87),(92), (93), (94), (98), (99), (122), (123), (124), (125), (126), (127),(128), (129), (130), (131), (132), (134), (135), (136),

the tautomers, the enantiomers, the diastereomers, the mixtures and thesalts of which are particularly preferred.

Within the scope of the present application, if applicable, by the terms“isomer”, “stereoisomer”, “diastereomer”, “enantiomer”, “chiral”,“racemate” or “racemic mixture” are meant the following. Compounds ofthe same empirical formula which differ in the nature or arrangement ofthe bonds of their atoms or their connectivity or the spatialarrangement of the atoms in the molecule, are referred to as “isomers”.Isomers which while having the same nature and type of connectivity oftheir atoms differ in the spatial arrangement of the atoms in themolecule and are not congruent are known as “stereoisomers”.

Stereoisomers which do not behave towards one another as image andmirror image are referred to as “diastereomers”, and stereoisomers whichdo behave towards one another as image and mirror image are referred toas “enantiomers”. When an asymmetrical centre or atom is present (alsoreferred to as stereocentre or chiral centre), for example in a carbonatom substituted by four different substituents, the molecule is“chiral” in nature and a pair of enantiomers are possible. An enantiomermay be characterised by the absolute configuration of its stereocentre.The absolute configuration is described using the descriptors (R) and(S), which are determined by applying the sequence rules according toCahn, Ingold and Prelog, or by describing the rotation of the plane ofpolarised light on interaction with the molecule, which is referred toas dextrorotatory or laevorotatory (i.e. with (+) or (−) as descriptor,accordingly). A chiral compound may occur both as an individualenantiomer or as a mixture of the corresponding enantiomers. A mixturewhich contains equal amounts of the two enantiomers of a compound isreferred to as a “racemate” or “racemic mixture”.

According to the invention the compounds of general formula (I) areobtained by methods known per se, for example by the following methods:

-   (a) In order to prepare a compound of general formula

-   -   wherein A, R¹ and R² are defined above:

-   1) preparing a compound of general formula (II), wherein X, A, R¹    and R² are defined above:

-   i) reducing the nitro group of a compound of general formula (III)

-   -   wherein X, A, R¹ and R² are as defined above.

The reduction of the nitro group is conveniently carried out for examplein a solvent or mixture of solvents such as water, aqueous ammoniumchloride solution, hydrochloric acid, sulphuric acid, phosphoric acid,formic acid, acetic acid, acetic anhydride with base metals such asiron, zinc, tin or sulphur compounds such as ammonium sulphide, sodiumsulphide or sodium dithionite or by catalytic hydrogenation withhydrogen, for example under a pressure of between 0.5 and 100 bar, butpreferably between 1and 50 bar, or with hydrazine as reducing agent,conveniently in the presence of a catalyst such as for example Raneynickel, palladium charcoal, platinum oxide, platinum on mineral fibresor rhodium, or with complex hydrides such as lithium aluminium hydride,sodium borohydride, sodium cyanoborohydride, diisobutylaluminiumhydride, conveniently in a solvent or mixture of solvents such as water,methanol, ethanol, isopropanol, pentane, hexane, cyclohexane, heptane,benzene, toluene, xylene, ethyl acetate, methylpropionate, glycol,glycoldimethylether, diethyleneglycoldimethylether, dioxane,tetrahydrofuran, N-methylpyrrolidinone, or N-ethyl-diisopropylamine,N-C₁₋₅-alkylmorpholine, N-C₁₋₅-alkylpiperidine, N-C₁₋₅-alkylpyrrolidine,triethylamine, pyridine, for example at temperatures between −30 and250° C., but preferably between 0 and 150° C.

The compounds of general formula (III) wherein X denotes a CH group maybe obtained as follows:

-   a) Selective oxidation of compounds of general formula (IV):

-   -   wherein A′ denotes a substituted cycloalkyleneimino group        optionally containing other heteroatoms, and R¹ and R² are as        defined above.

The oxidation of a methylene group adjacent to the nitrogen is carriedout for example with oxidising agents such as potassium permanganate,potassium chromate, potassium dichromate, chromium(VI)oxide,mercury(II)chloride, selenium(IV)oxide, lead(IV)oxide, lead(II,IV)oxide,potassium peroxomonosulphate, hydrogen peroxide, sodium hypochlorite,optionally in the presence of a suitable catalyst such asnickel(II)chloride, cobalt(II)chloride, ruthenium(III)chloride,osmium(VIII)oxide, vanadium(IV)oxide and/or in the presence of a crownether such as 18-crown-6, in a solvent or mixture of solvents such aswater, formic acid, acetic acid, ethyl acetate, benzene, pyridine,dichloromethane, chloroform, tetrachloromethane, optionally under2-phase conditions in the presence of a suitable phase transfer catalystsuch as for example tetrabutylammonium chloride, tetrabutylammoniumbromide, benzyl-triethyl-ammonium chloride or methyl-trioctyl-ammoniumchloride, optionally in the presence of an acid such as acetic acid,hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid,sodium hydrogen sulphate, sodium dihydrogen phosphate and/or a base suchas sodium hydroxide, potassium hydroxide, ammonia, pyridine, potassiumphosphate, dipotassium hydrogen phosphate or sodium acetate attemperatures between −30 and 250° C., but preferably between 0 and 150°C. For example this reaction may be carried out as described in J. H.Markgraf, C. A. Stickney, J. Heterocycl. Chem. 2000, 37(1), 109.

The compounds of general formula (IV) may be obtained as follows:

-   a)i) Nucleophilic substitution with a compound of general formula    A′-H  (V),    -   wherein A′ denotes a cycloalkyleneimino group optionally        containing further heteroatoms, at the aromatic group of general        formula

-   -   wherein R¹ and R² are as defined above.

The nucleophilic substitution is conveniently carried out in a solventor mixture of solvents such as ethanol, isopropanol, benzene,chlorobenzene, toluene, xylene, glycol, glycoldimethylether,diethyleneglycoldimethylether, dimethylformamide, N-methylpyrrolidinone,tetralin, dimethylsulphoxide, sulpholane, methylene chloride,chloroform, tetrachloromethane or N-ethyl-diisopropylamine,N-C₁₋₅-alkylmorpholine, N-C₁₋₅-alkylpiperidine, N-C₁₋₅-alkylpyrrolidine,triethylamine, pyridine, for example at temperatures between −30 and250° C., but preferably between 0 and 150° C., if desired convenientlyin the presence of bases such as potassium carbonate, sodium carbonate,potassium-tert.-butoxide, sodium ethoxide, potassiumhexamethyldisilazane, sodium hydride or lithium diisopropylamide.

-   a)ii) Transition metal-catalysed coupling reaction of a compound of    general formula    A′-H  (V)    -   wherein A′ denotes a cycloalkyleneimino group optionally        containing further heteroatoms, at the aromatic group of general        formula

-   -   wherein R¹ and R² are as defined above and Z¹ denotes a        chlorine, bromine or iodine atom or a triflate group.

The reaction is expediently carried out in a solvent or mixture ofsolvents such as benzene, toluene, xylene, tetrahydrofuran, dioxane,diethyl ether, tert.-butyl-methyl-ether, ethyleneglycoldimethylether,diethyleneglycoldimethylether, sulpholane, dimethylformamide,N-methylpyrrolidinone, tetralin, dimethylsulphoxide, methylene chloride,chloroform or tetrachloromethane, for example at temperatures between−30 and 250° C., but preferably between 0 and 150° C., conveniently inthe presence of transition metal catalysts such as nickel on activatedcharcoal, palladium charcoal,tetrakis-(triphenylphosphine)-palladium(0),tris-(dibenzylideneacetone)-dipalladium(0), palladium(II)acetate,palladium(II)chloride, bis-(triphenylphosphine)-palladium(II)-chloride,bis-(tricyclohexylphosphine)-palladium(II)-chloride,bis-(triethylphosphine)-palladium(II)-chloride,bis-(tri-o-tolylphosphine)-palladium(II)-chloride, optionally in thepresence of ligands such as triphenylphosphine, tri-o-tolylphosphine,tri-tert.-butylphosphine, 1,3-bis-(diphenylphosphino)-propane,2,2′-bis-(diphenyl-phosphino)-1,1′-dinaphthyl,1,1′-bis-(diphenylphosphino)-ferrocene, Xantphos, and conveniently inthe presence of a base such as sodium methoxide, sodium ethoxide,sodium-tert.-butoxide, potassium-tert.-butoxide,sodium-tert.-butyldimethyl-silanoate, potassium hexamethyldisilazane,lithium diisopropylamide, potassium carbonate, rubidium carbonate,caesium carbonate, potassium phosphate, sodium hydride, optionally inthe presence of a complexing agent such as 18-crown-6-ether as well asconveniently using an inert gas atmosphere (for example nitrogen orargon) and optionally under pressure.

-   b) Acylation/sulphonylation and alkylation of a compound of general    formula

-   -   wherein R¹ and R² are as defined above, with a compound of        general formula

-   -   wherein E denotes a carbonyl, oxycarbonyl, sulphonyl or a        sulphamoyl group optionally substituted at the nitrogen atom as        mentioned above, G denotes a chlorine, bromine or iodine atom or        an anhydride, C₁₋₅-alkoxy or benzotriazoloxy group or E and G        together denote an isocyanato or cyano group and Z⁴ denotes a        nucleofugic leaving group, for example a chlorine, bromine or        iodine atom, a tosylate, triflate or mesylate group, and n is a        number between 2 and 5, while individual methylene groups as        described above may additionally be substituted or replaced by        heteroatoms, and subsequent intramolecular cyclisation by        alkylation of the anilidic nitrogen, thereby cleaving the        nucleofugic leaving group Z⁴.

The acylation/sulphonylation is conveniently carried out in a solvent ormixture of solvents such as benzene, chlorobenzene, toluene, xylene,glycoldimethylether, diethyleneglycoldimethylether, dimethylformamide,N-methylpyrrolidinone, tetralin, dimethylsulphoxide, sulpholane,methylene chloride, chloroform, tetrachloromethane,N-ethyl-diisopropylamine, N-C₁₋₅-alkylmorpholine,N-C₁₋₅-alkylpiperidine, N-C₁₋₅-alkylpyrrolidine, triethylamine,pyridine, for example at temperatures between −30 and 250° C., butpreferably between 0 and 150° C., conveniently in the presence of basessuch as pyridine, triethylamine, p-dimethylaminopyridine, potassiumcarbonate, sodium carbonate, potassium-tert.-butoxide, sodium methoxide,sodium ethoxide or basic ion exchanger.

The subsequent intramolecular alkylation is conveniently carried out ina solvent or mixture of solvents such as benzene, chlorobenzene,toluene, xylene, glycoldimethylether, diethyleneglycoldimethylether,dimethylformamide, dimethylsulphoxide, sulpholane, methylene chloride,tetrachloromethane, N-ethyl-diisopropylamine, N-C₁₋₅-alkylmorpholine,N-C₁₋₅-alkylpiperidine, N-C₁₋₅-alkylpyrrolidine, triethylamine,pyridine, for example at temperatures between −30 and 250° C., butpreferably between 0 and 150° C., conveniently in the presence of basessuch as pyridine, triethylamine, potassium carbonate, sodium carbonate,potassium-tert.-butoxide, sodium methoxide, sodium ethoxide, sodiumhydride, potassium hexamethyldisilazane or lithium diisopropylamide.

-   c) Nucleophilic substitution with a compound of general formula

-   -   wherein Y¹ denotes a hydroxyl, amino or thiol function        optionally blocked by a corresponding protective group and n is        a number between 2 and 4, at the aromatic group of general        formula

-   -   wherein R¹ and R² are as defined above, and subsequent        cyclisation by reaction with a compound of general formula

-   -   wherein Z² and Z³ denote nucleofugic leaving groups such as        chlorine, bromine or iodine atoms or triflate, mesylate or        tosylate groups, E denotes the carbonyl or sulphonyl group and n        is a number between 0 and 4, while individual methylene groups        may be substituted as described above or may be replaced by        optionally substituted heteroatoms or other groupings.

The initial nucleophilic aromatic substitution is carried out forexample as described under (a) 1) i) a)i). It is optionally followed bythe unblocking of the nucleophilic group Y¹ by methods known from theliterature or as generally described hereinafter.

The reaction of the resulting compound with the compound of generalformula (X) is conveniently carried out in a solvent or mixture ofsolvents such as benzene, chlorobenzene, toluene, xylene,glycoldimethylether, diethyleneglycoldimethylether, dimethylformamide,N-methylpyrrolidinone, tetralin, dimethylsulphoxide, sulpholane,methylene chloride, chloroform, tetrachloromethane,N-ethyl-diisopropylamine, N-C₁₋₅-alkylmorpholine,N-C₁₋₅-alkylpiperidine, N-C₁₋₅-alkylpyrrolidine, triethylamine,pyridine, for example at temperatures between −30 and 250° C., butpreferably between 0 and 150° C., conveniently in the presence of basessuch as pyridine, triethylamine, p-dimethylaminopyridine, potassiumcarbonate, sodium carbonate, potassium-tert.-butoxide, sodium methoxide,sodium ethoxide or basic ion exchanger.

-   d) Alkylation and subsequent acylation/sulphonylation of a compound    of general formula

-   -   wherein R¹ and R² are as defined above, with a compound of        general formula

-   -   wherein E denotes a carbonyl, oxycarbonyl, sulphonyl or a        sulphamoyl group optionally substituted at the nitrogen atom of        a as mentioned above, G denotes a chlorine, bromine or iodine        atom or an anhydride, C₁₋₅-alkoxy or benzotriazoloxy group or E        and G together denote an isocyano group and Z⁴ denotes a        nucleofugic leaving group, for example a chlorine, bromine or        iodine atom, a tosylate, triflate or mesylate group, and n is a        number between 2 and 5, while individual methylene groups        according to the description given above may additionally be        substituted or replaced by heteroatoms, and subsequent        intramolecular cyclisation by alkylation of the anilide        nitrogen, thereby cleaving the nucleofugic leaving group Z⁴.

The alkylation is conveniently carried out in a solvent or mixture ofsolvents such as benzene, chlorobenzene, toluene, xylene,glycoldimethylether, diethyleneglycoldimethylether, dimethylformamide,dimethylsulphoxide, sulpholane, methylene chloride, tetrachloromethane,N-ethyl-diisopropylamine, N-C₁₋₅-alkylmorpholine,N-C₁₋₅-alkylpiperidine, N-C₁₋₅-alkylpyrrolidine, triethylamine,pyridine, for example at temperatures between −30 and 250° C., butpreferably between 0 and 150° C., conveniently in the presence of basessuch as pyridine, triethylamine, potassium carbonate, sodium carbonate,potassium-tert.-butoxide, sodium methoxide, sodium ethoxide, sodiumhydride, lithium, sodium, potassium hexamethyldisilazane or lithiumdiisopropylamide. The subsequent intramolecular acylation/sulphonylationis conveniently carried out in a solvent or mixture of solvents such asbenzene, chlorobenzene, toluene, xylene, glycoldimethylether,diethyleneglycoldimethylether, dimethylformamide, N-methylpyrrolidinone,tetralin, dimethylsulphoxide, sulpholane, methylene chloride,chloroform, tetrachloromethane, N-ethyl-diisopropylamine,N-C₁₋₅-alkylmorpholine, N-C₁₋₅-alkylpiperidine, N-C₁₋₅-alkylpyrrolidine,triethylamine, pyridine, for example at temperatures between −30 and250° C., but preferably between 0 and 150° C., conveniently in thepresence of bases such as pyridine, triethylamine,p-dimethylaminopyridine, potassium carbonate, sodium carbonate,potassium-tert.-butoxide, sodium methoxide, sodium ethoxide or basic ionexchanger.

-   e) Sequential alkylation of a compound of general formula

-   -   wherein R¹ and R² are as defined above, with a compound of        general formula

-   -   wherein Z⁵ denotes a nucleofugic leaving group such as for        example a bromine or chlorine atom or a tosylate, triflate or        mesylate group, Y¹ denotes a nucleophilic group, optionally        blocked by a suitable protective group, such as a hydroxy group        or an amino group optionally substituted as described        hereinbefore and m is a number between 2 and 5, while individual        methylene groups as described abovemay additionally be        substituted or replaced by heteroatoms,    -   with subsequent acylation/sulphonylation with a compound of        general formula

-   -   wherein E denotes a carbonyl, oxycarbonyl, sulphonyl or a        sulphamoyl group optionally substituted at the nitrogen atom of        a as mentioned above, G denotes a chlorine, bromine or iodine        atom or an anhydride, C₁₋₅-alkoxy or benzotriazoloxy group or E        and G together denote an isocyanato or cyano group and Z⁴        denotes a nucleofugic group, for example a bromine or chlorine        atom or a tosylate, triflate or mesylate group, and n is a        number between 2 and 5, while individual methylene groups        according to the description given above may additionally be        substituted or replaced by heteroatoms,    -   and subsequent intramolecular cyclisation by alkylation of the        optionally previously unblocked nucleophilic group Y¹, thereby        cleaving the nucleofugic leaving group Z⁴.

Both the necessary alkylations and the acylation/sulphonylation may becarried out analogously to the conditions described under (a)1)i)b) or(a)1)i) d).

-   f) Carbamoylation/urea formation with a compound of general formula

-   -   wherein R¹ and R² are as defined above, and which may be        obtained by methods known from the literature from compounds of        general formula (VIII), for example by reacting with phosgene in        toluene, with a compound of general formula

-   -   wherein Z⁶ denotes a nucleofugic leaving group, for example a        chlorine, bromine or iodine atom, a tosylate, triflate or        mesylate group, and E denotes a hydroxyl, amino or        C₁₋₃-alkylamino function and n is a number between 2 and 4,        while individual methylene groups may additionally be        substituted as described above, and subsequent intramolecular        cyclisation by alkylation of the anilidic nitrogen, thereby        cleaving the nucleofugic leaving group Z⁶.

The carbamoylation is conveniently carried out in a solvent or mixtureof solvents such as benzene, chlorobenzene, toluene, xylene,glycoldimethylether, diethyleneglycoldimethylether, dimethylformamide,N-methylpyrrolidinone, tetralin, dimethylsulphoxide, sulpholane,methylene chloride, chloroform, tetrachloromethane,N-ethyl-diisopropylamine, N-C₁₋₅-alkylmorpholine,N-C₁₋₅-alkylpiperidine, N-C₁₋₅-alkylpyrrolidine, triethylamine,pyridine, for example at temperatures between −30 and 250° C., butpreferably between 0 and 150° C. The subsequent intramolecularalkylation is carried out for example analogously to the description in(a)1)i)b).

-   ii) Transition metal-catalysed coupling reaction of a compound of    general formula    A-H  (XV),    -   wherein A is as defined above, at the aromatic group of general        formula

-   -   wherein X, R¹ and R² are as defined above and Z¹ denotes a        chlorine, bromine or iodine atom or a triflate group.

The reaction is expediently carried out in a solvent or mixture ofsolvents such as benzene, toluene, xylene, tetrahydrofuran, dioxane,diethyl ether, tert.-butyl-methyl-ether, ethyleneglycoldimethylether,diethyleneglycoldimethylether, sulpholane, dimethylformamide,N-methylpyrrolidinone, tetralin, dimethylsulphoxide, methylene chloride,chloroform or tetrachloromethane, for example at temperatures between−30 and 250° C., but preferably between 0 and 200° C., conveniently inthe presence of transition metal catalysts such astetrakis-(triphenylphosphine)-palladium(0),tris-(dibenzylideneacetone)-dipalladium(0), palladium(II)acetate,palladium(II)chloride, bis-(triphenylphosphine)-palladium(II)-chloride,bis-(tricyclohexylphosphine)-palladium(II)-chloride,bis-(triethylphosphine)-palladium(II)-chloride,bis-(tri-o-tolylphosphine)-palladium(II)-chloride, optionally in thepresence of ligands such as triphenylphosphine, tri-o-tolylphosphine,tri-tert.-butylphosphine, 1,3-bis-(diphenylphosphino)-propane,2,2′-bis-(diphenylphosphino)-1,1′-dinaphthyl,1,1′-bis-(diphenylphosphino)-ferrocene, Xantphos, or for example in thepresence of a transition metal catalyst such as copper(I)-iodide,copper(I)-bromide or copper(I)-acetate and conveniently in the presenceof a base such as tetramethylguanidine, tetramethylethylenediamine orN,N′-dimethylethylenediamine and conveniently in the presence of a basesuch as sodium methoxide, sodium ethoxide, sodium-tert.-butoxide,potassium-tert.-butoxide, sodium-tert.-butyldimethyl-silanoate,potassium hexamethyldisilazane, lithium diisopropylamide, potassiumcarbonate, rubidium carbonate, caesium carbonate, potassium phosphate,sodium hydride, optionally in the presence of a complexing agent such as18-crown-6-ether as well as conveniently using an inert gas atmosphere(for example nitrogen or argon) and optionally under pressure.

-   iii) Ring-closing metathesis of a compound of general formula

-   -   wherein X, R¹ and R² are as defined above, Z⁷ denotes an        optionally substituted amino group or the nitro group, E denotes        an aminocarbonyl, aminosulphonyl group or a carbonyl or        sulphonyl group optionally substituted as described above, while        l and o independently of one another denote identical or        different numbers between 1and 3 which may be obtained by a        sequence of alkylation and        acylation/sulphonylation/carbamoylation/sulphamoylation with        corresponding reagents using the methods already described in        (a)1)i)c), for example, or by other methods known from the        literature, optionally followed by reduction, if Z⁷ denotes a        nitro group, using the procedure described under (a)1)i)

The ring closing metathesis reaction is conveniently carried out in asolvent or mixture of solvents such as benzene, chlorobenzene, toluene,xylene, methanol, ethanol, propanol, diethyl ether,tert.-butyl-methyl-ether, tetrahydrofuran, dioxane, glycoldimethylether,diethyleneglycoldimethylether, dimethylformamide, N-methylpyrrolidinone,tetralin, dimethylsulphoxide, sulpholane, methylene chloride,chloroform, tetrachloromethane, pyridine, in the presence of a catalystsuch as benzylidene-bis-(tricyclohexylphosphine)-dichloro-ruthenium (1stgeneration Grubbs catalyst) orbenzylidene-[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene]-dichloro-(tricyclo-hexylphosphine)-ruthenium(2nd generation Grubbs catalyst) for example at temperatures between −30and 250° C., but preferably between 0 and 150° C., conveniently under aninert gas atmosphere, for example argon.

-   2) Preparation of a compound of general formula (II), wherein X, R¹    and R² are as defined above and which contain, according to the    definition of A, thiocarbonyl or optionally correspondingly    substituted imino groups in the ring:-   i) thionylation of the corresponding carbonyl-analogous compound of    general formula (XV), optionally followed by alkylation of the    sulphur and reaction with a correspondingly substituted amine (for    example methylamine, hydroxylamine, acetoxyamine, methoxyamine,    cyanamide or corresponding analogous compounds), and subsequent    coupling of the compound obtained with a compound of general    formula (XVI) according to the description of (a)1)ii)

The thionation is conveniently carried out, for example, in a solvent ormixture of solvents such as pentane, hexane, cyclohexane, heptane,benzene, toluene, xylene, glycoldimethylether,diethyleneglycoldimethylether, dioxane, tetrahydrofuran,dichloromethane, chloroform, tetrachloromethane, 1,2-dichloroethane,N-methylpyrrolidinone, or N-ethyl-diisopropylamine,N-C₁₋₅-alkylmorpholine, N-C₁₋₅-alkylpiperidine, N-C₁₋₅-alkylpyrrolidine,triethylamine, pyridine, with reagents such as for example phosphoruspentasulphide,2,2-bis-(4-methoxy-phenyl)-1,3,2,4-dithiadiphosphetane-2,4-disulphide(Lawesson's reagent) or mixtures of reagents such as for examplephosphorus oxychloride followed by 1,1,1,3,3,3-hexamethyldisilathiane,trifluorosulphonic anhydride followed by hydrogen sulphide, or themixture of hydrogen sulphide, chlorotrimethylsilane andlithium-diisopropylamide, optionally in the presence of a base such aspotassium carbonate, sodium carbonate, sodium hydrogen carbonate,pyridine, triethylamine, for example at temperatures between −30 and250° C., but preferably between −10 and 150° C. Any subsequentalkylation of the corresponding thiocarbonyl compounds is convenientlycarried out for example in a solvent or mixture of solvents such aspentane, hexane, cyclohexane, heptane, benzene, toluene, xylene,glycoldimethylether, diethyleneglycoldimethylether, dioxane,tetrahydrofuran, dichloromethane, chloroform, tetrachloromethane,1,2-dichloroethane, chlorobenzene, pyridine, water, methanol, ethanol,n-propanol, iso-propanol, n-butanol, acetone, butanone, acetonitrile ornitromethane, optionally under 2-phase conditions with the addition of aphase transfer catalyst such as tetrabutyl-ammonium-chloride,tetrabutyl-ammonium-bromide, methyl-trioctyl-ammonium-chloride orAliquat 336 with reagents such as for example methyl iodide,ethylbromide, dimethylsulphate, diethylsulphate ortrimethyloxonium-tetrafluoroborate, conveniently optionally in thepresence of a base such as potassium carbonate, sodium carbonate, sodiumhydrogen carbonate, pyridine, triethylamine, N-ethyl-diisopropylamine,N-C₁₋₅-alkylmorpholine, N-C₁₋₅-alkylpiperidine, N-C₁₋₅-alkylpyrrolidine,for example at temperatures between −30 and 250° C., but preferablybetween −10 and 150° C. The reaction with an amino compound to preparethe corresponding imine, following an alkylation, is convenientlycarried out for example in a solvent or mixture of solvents such aspentane, hexane, cyclohexane, heptane, benzene, toluene, xylene,glycoldimethylether, diethyleneglycoldimethylether, dioxane,tetrahydrofuran, dichloromethane, chloroform, tetrachloromethane,1,2-dichloroethane, chlorobenzene, pyridine, water, methanol, ethanol,n-propanol, iso-propanol, n-butanol, acetone, butanone, acetonitrile ornitromethane, with corresponding reagents depending on the substitutionof the imine, such as for example ammonia, sodium amide, hydroxylamine,methoxyamine, ethoxyamine, propoxyamine acetoxyamine or cyanamide,optionally in the presence of a base such as sodium hydride, potassiumhydride, potassium carbonate, sodium carbonate, sodium hydrogencarbonate, pyridine, triethylamine and optionally under pressure, attemperatures between −30 and 250° C., but preferably between −20 and120° C., for example.

-   ii) Thionylation of the corresponding carbonyl-analogous compound of    general formula (III), which may be obtained by the methods    described under (a)1)i)a), b), c), d) and e), optionally followed by    alkylation of the sulphur and reaction with a correspondingly    substituted amine (for example methylamine, hydroxylamine,    acetoxyamine, methoxyamine, cyanamide or corresponding analogous    compounds), and subsequent reduction of the nitro group by the    methods described in (a)1)i), optionally followed by reductive    amination according to the methods described under (a)2).

The thionylation and the reaction of alkylation and imine formationwhich optionally follows may be carried out analogously to the methodsdescribed under (a)3)i).

-   iii) thionylation of the corresponding carbonyl-analogous compound    of general formula (II), which may be obtained according to the    processes described in (a)1)i), ii), iii) and (a)2), optionally    followed by alkylation of the sulphur and reaction with a    correspondingly substituted amine (for example methylamine,    hydroxylamine, acetoxyamine, methoxyamine, cyanamide or    corresponding analogous compounds), while during any subsequent    alkylation the aniline amino group present is conveniently blocked    by suitable protective groups which are cleaved after the reaction    to form the imine.

The thionylation and the reaction of alkylation and imine formationwhich optionally follows may be carried out analogously to the methodsdescribed under (a)3)i).

-   3) Preparation of a compound of general formula (II), wherein X, R¹    and R² are as defined above and contain the imino groups optionally    substituted according to the definition for A in the ring:-   i) alkylation of the carbonyl-analogous compounds of general    formula (XV) and subsequent reaction with a correspondingly    substituted amine (for example methylamine, hydroxylamine,    acetoxyamine, methoxyamine, cyanamide or corresponding analogous    compounds), and subsequent coupling of the resulting compound with a    compound of general formula (XVI) according to description (a)1)ii)

The alkylation and the subsequent reaction with an amino compound inorder to prepare the corresponding imine may be carried out as describedunder (a)3) i).

-   ii) alkylation of the carbonyl-analogous compounds of general    formula (III), which may be obtained according to the processes    described in (a)1)i) a), b), c), d) and e), and subsequent reaction    with a correspondingly substituted amine (for example methylamine,    hydroxylamine, acetoxyamine, methoxyamine, cyanamide or    corresponding analogous compounds), and subsequent reduction of the    nitro group by the methods described in (a)1)i), optionally with    subsequent reductive amination by the methods described in (a)2).

The alkylation and the subsequent reaction with an amino compound inorder to prepare the corresponding imine may be carried out as describedunder (a)3) i).

-   (b) In order to prepare a compound of general formula

-   -   wherein Z⁹ denotes a protective group of the amino function        which may subsequently be cleaved by methods known from the        literature, and R³ to R⁵ are as defined above:

-   1) reduction and subsequent lactonisation of a compound of general    formula

-   -   wherein Z⁹ denotes a protective group for the amino function        which may subsequently be cleaved by methods known from the        literature, and R³ to R⁵ are as defined above:

The reduction to the intermediate hydroxy acid is for exampleconveniently carried out in a solvent or mixture of solvents such astetrahydrofuran, dioxane, glycoldimethylether,diethyleneglycoldimethylether, pentane, hexane, cyclohexane, heptane,benzene, toluene or xylene with complex hydrides such as sodiumborohydride, lithium borohydride, sodium cyanoborohydride, for example,at temperatures between −80 and 250° C., but preferably between −30 and150° C.

The subsequent lactonisation of the intermediate is conveniently carriedout for example in a solvent or mixture of solvents such as benzene,chlorobenzene, toluene, xylene, dichloromethane, chloroform,tetrachloromethane, 1,2-dichloroethane in the presence of a catalystsuch as para-toluenesulphonic acid, camphorsulphonic acid or acidic ionexchanger, optionally in the presence of a drying agent such as sodiumsulphate, magnesium sulphate or molecular sieves, for example attemperatures between −30 and 250° C., but preferably at temperaturesbetween 0 and 200° C. This reaction may, for example, be carried out asdescribed by G. J. McGarvey, J. M. Williams, R. N. Hiner, Y. Matsubara,T. Oh J. Am. Chem. Soc. 1986, 108, 4943-4952.

-   2) (Sequential) alkyation of a compound of general formula

-   -   wherein R³ is as defined above and Z¹⁰ denotes a protective        group for the amino function which may subsequently be cleaved        by methods known from the literature, but also an acyl group of        formula

-   -   wherein B is as defined above,    -   with a compound of general formula        T-Z¹¹  (XXI),    -   wherein the group T denotes the groups R⁴ or R⁵ as defined        above, with the proviso that T may not represent the group OR⁹,    -   and Z¹¹ denotes a nucleofugic group, for example an iodine,        bromine or chlorine atom or a tosylate, triflate or mesylate        group:

The alkyation may be repeated with a similar or different alkylatingagent of formula (XXI), so as to obtain □,□-disubstituted lactones ofthe compound (XVIII).

The alkylations may be carried out analogously to the conditionsdescribed under (a)1)i) b) or as described in A. El Hadri, A.Ahbouabdellah, U. Thomet, R. Baur, R. Furtmüller, E. Sigel, W. Sieghart,R. H. Dodd, J. Med. Chem. 2002, 45, 2824-2831.

-   3) Nucleophilic Substitution of a Compound of General Formula

-   -   wherein Z¹² denotes a nucleofugic group, for example an iodine,        bromine or chlorine atom or a tosylate, triflate or mesylate        group, and R⁴ and R⁵ are as defined above,    -   with a compound selected for example from among lithium, sodium,        potassium azide, sodium, potassium phthalimide,        4-methoxybenzylamine, benzylamine, 2,4-dimethoxybenzylamine,        dibenzylamine, potassium or sodium cyanide,    -   and subsequent reduction of the group thus introduced and        treatment of the protective group

The nucleophilic substitution is conveniently carried out in a solventor mixture of solvents such as ethanol, isopropanol, benzene,chlorobenzene, toluene, xylene, glycol, glycoldimethylether,diethyleneglycoldimethylether, dimethylformamide, N-methylpyrrolidinone,tetralin, dimethylsulphoxide, sulpholane, methylene chloride,chloroform, tetrachloromethane or N-ethyl-diisopropylamine,N-C₁₋₅-alkylmorpholine, N-C₁₋₅-alkylpiperidine, N-C₁₋₅-alkylpyrrolidine,triethylamine, pyridine, for example at temperatures between −30 and250° C., but preferably between 0 and 150° C., optionally convenientlyin the presence of bases such as lithium, sodium, potassium, caesiumcarbonate, potassium-tert.-butoxide, sodium ethoxide, potassiumhexamethyldisilazane, sodium hydride or lithium diisopropylamide. Forexample this reaction may be carried out as described by R. N.Salvatore, A. S. Nagle, K. W. Jung, J. Org. Chem. 2002, 67, 674-683.

The subsequent reduction of the nitrogen nucleophil thus introduced iscarried out for example analogously to the description under (a)1).

The aminolactone thus obtained is provided with a protective group, forexample, by methods known from the literature.

Compounds of formula (XXII) may be prepared, for example, from malonicacids as described by J.-L. Canet, A. Fadel, J. Salaun, J. Org. Chem.1992, 57, 3463-3473.

-   (c) In order to prepare a compound of general formula

-   -   wherein A, X and R¹ to R³ are as defined above:    -   tandem Michael addition/lactamisation of a compound of general        formula

-   -   wherein A, X, R¹ and R² are as defined above,    -   with itaconic acid and    -   optionally a subsequent sequence of esterification,    -   □-alkylation with a compound of general formula        T¹-Z¹¹  (XXIV),    -   wherein T¹ denotes a C₁₋₃-alkyl group and Z¹¹ denotes a        nucleofugic group, for example an iodine, bromine or chlorine        atom or a tosylate, triflate or mesylate group, and unblocking        of the carboxylic acid:

The tandem Michael addition/lactamisation is conveniently carried outwith itaconic acid at a temperature of 50-250° C., but preferably at80-200° C., in the presence or absence of a solvent or mixture ofsolvents such as water, ethanol, propanol, butanol, toluene, xylene,chlorobenzene, tetralin, diphenylether. This reaction makes it possibleto synthesise compounds of general formula (XXIII) with the proviso thatR³ denotes a hydrogen atom. Optional subsequent substitution is preparedfor by blocking the carboxylic acid function by esterification usingmethods known from the literature.

The alkylation may be carried out analogously to the conditionsdescribed under (a)1)i) b) or as described by X.-H. Jiang, Y.-L. Song,Y.-Q. Long, Bioorg. Med. Chem. Lett. 2004, 14, 3675-3678.

The unblocking of the esterified carboxylic acid by methods known fromthe literature makes it possible to prepare □-substituted carboxylicacids of general formula (XXIII), wherein R³ then also denotes aC₁₋₃-alkyl group.

-   (d) In order to prepare a compound of general formula

-   -   wherein A, X and R¹ to R⁵ are as defined above:

-   1) Transition metal-catalysed coupling reaction of a compound of    general formula

-   -   wherein A, X, R¹ and R² are as defined above and Z¹ denotes a        chlorine, bromine or iodine atom or a triflate group, with    -   a compound of general formula

-   -   wherein R³ to R⁵ are as defined above and Z¹⁵ denotes a        protective group for the hydroxy function, and    -   subsequent unblocking of the hydroxy function:

The coupling reaction may for example be carried out analogously to theconditions described under (a)1)a)ii).

The unblocking of the hydroxy function may be carried out using methodsknown from the literature.

The compounds of general formula (XXVI) may be prepared from thecorresponding amines of general formula (II) by methods known from theliterature such as for example the Sandmeyer reaction.

-   (e) In order to prepare a compound of general formula

-   -   wherein A, X and R¹ to R⁵ are as defined above and Z¹³ denotes a        protective group for the amino function, which may subsequently        be cleaved using methods known from the literature, but may also        denote an acyl group of formula

-   -   wherein B is as defined above:    -   Lewis acid-assisted lactone opening of a compound of general        formula

-   -   wherein R³ to R⁵ are as defined above and Z¹³ denotes a        protective group for the amino function, which may subsequently        be cleaved using methods known from the literature, but may also        denote an acyl group of formula

-   -   wherein B is as defined above,    -   with a compound of general formula

-   -   wherein A, X, R¹ and R² are as defined above:

The compound of general formula (II) is activated with anorganoaluminium compound such as for example trimethylaluminium,triethylaluminium, tripropylaluminium, triisobutylaluminium,tributylaluminium, triphenylaluminium in a solvent or mixture ofsolvents such as dichloromethane, toluene, xylene, benzene, hexane,cyclohexane, heptane, tetrahydrofuran, at a temperature of −100 to 100°C., but preferably between −80 and 80° C., and reacted with the lactoneof general formula (XXIX).

-   (f) In order to prepare a compound of general formula

-   -   wherein A, X and R¹ to R⁵ are as defined above:

-   1) Nucleophilic Ring Opening of a Compound of General Formula

-   -   wherein A, X, R¹ and R² are as defined above,    -   with an alkali metal salt of the compound R⁹OH,    -   wherein R⁹ is as defined above:

The nucleophilic ring opening of the carbamate to form the free amine isconveniently carried out in a solvent or mixture of solvents such aswater, methanol, ethanol, isopropanol, pentane, hexane, cyclohexane,heptane, benzene, toluene, xylene, glycol, glycoldimethylether,diethyleneglycol dimethylether, dioxane, tetrahydrofuran,N-methylpyrrolidinone, dimethylformamide with the lithium, sodium orpotassium salt of the compound R⁹OH, for example at temperatures between−30 and 250° C., but preferably between 0 and 150° C.

The compounds of formula (XXXI) may for example be prepared as describedby T. Kametani, Y. Kigawa, M. Ihara, tetrahedron. 1979, 35, 313-316.

-   2) Acid breakdown reaction of a compound of general formula

-   -   wherein A, X, R¹ to R³ are as defined above:

The carboxylic acids are converted into, for example, activatedcarbonylamides or carbonylazides by methods known from the literature.By a rearrangement reaction (for example Hofmann, Lossen or Curtiusrearrangement) these intermediates are converted into isocyanates.

The isocyanates thus formed are converted by reaction with an alcoholinto the carbamates conventionally used as protective groups for theamine function. These carbamate protective groups are subsequentlycleaved using methods known from the literature and free the amine offormula (XXX).

The isocyanates may optionally also be converted directly into the amineof formula (XXX) under the effect of aqueous acid are.

The preparation of the activated carboxylic acid derivatives may forexample be carried out by activation of the above-mentioned carboxylicacids of formula (XXIII) as carbonylhalides or as asymmetric anhydrideswith subsequent reaction with lithium, sodium, potassium azide orhydrazine or hydroxylamine in a solvent or mixture of solvents such asacetone, butanone, water, dimethylformamide, benzene, toluene, xylene,chlorobenzene, acetonitrile, nitromethane, tetrahydrofuran, dioxane,glycoldimethylether, diethyleneglycol dimethylether, dimethylformamide,N-methylpyrrolidinone, dimethylsulphoxide, sulpholane, methylenechloride, chloroform, tetrachloromethane, optionally in the presence ofa base such as for example N-ethyl-diisopropylamine,N-C₁₋₅-alkylmorpholine, N-C₁₋₅-alkylpiperidine, N-C₁₋₅-alkylpyrrolidine,triethylamine, pyridine at temperatures between −80 and 250° C., butpreferably between −30 and 150° C.

The acid breakdown reaction (i.e. rearrangement to form the isocyanateand carbamate formation) starting from the carboxylic acid of formula(XXIII) is conveniently carried out with diphenylphosphorylazide and abase such as for example N-ethyl-diisopropylamine,N-C₁₋₅-alkylmorpholine, N-C₁₋₅-alkylpiperidine, N-C₁₋₅-alkylpyrrolidine,triethylamine, pyridine, in a solvent or mixture of solvents such asbenzene, toluene, chlorobenzene, xylene, tetrahydrofuran, dioxane,glycol dimethylether, diethyleneglycol dimethylether, dimethylformamide,N-methylpyrrolidinone, dimethylsulphoxide, sulpholane, methylenechloride, chloroform or tetrachloromethane at temperatures between −30and 250° C., but preferably between 0 and 200° C., in the presence of analcohol such as for example tert.-butanol, benzylalcohol,para-methoxybenzylalcohol, fluorenylmethanol.

These carbamate protective groups are subsequently cleaved using methodsknown from the literature and free the amine of formula (XXX).

-   3) Mitsunobu cyclodehydration and subsequent cleaving of the    protective groups from a compound of general formula

-   -   wherein A, X and R¹ to R⁵ are as defined above and Z¹⁴ denotes a        protective group for the amino function:

The lactamisation under Mitsunubo conditions is conveniently carried outin an inert solvent or mixture of solvents such as for exampletetrahydrofuran, dioxane, benzene, toluene, xylene, acetonitrile in thepresence of phosphines such as for example triphenylphosphine,tributylphosphine with dialkylazodicarboxylates such as for examplediethyl azodicarboxylate, diisopropyl azodicarboxylate, di(tert.-butyl)azodicarboxylate, for example at a temperature of −50 to 200° C., butpreferably between −20 and 150° C. The subsequent unblocking of theamino function may be carried out using methods described in theliterature.

-   4) reduction of the aromatic nitro group, subsequent conversion of    the amino group thus freed into the group A as defined above and    cleaving of the protective group from a compound of general formula

-   -   wherein X and R¹ to R⁵ are as defined above and Z¹⁶ denotes a        protective group for the amino function:

The reduction of the nitro group may be carried out analogously to theconditions described in (a)1)i).

The subsequent conversion of the amino group thus freed into the group Aas defined above may for example be carried out analogously to theconditions described in (a)1)i)b)-f).

The subsequent unblocking of the amino function may be carried out usingmethods described in the literature.

The compounds of general formula (XXXIII) may be prepared analogously tothe conditions described in (e) or (f) 3) from compounds of generalformula

-   -   wherein X, R¹ and R² are as defined above,        or    -   from compounds of general formula

-   -   wherein X and R¹ to R³ are as defined above and Z¹⁶ denotes a        protective group for the amino function,    -   by (sequential) alkylation analogously to the conditions        described in (a) 1)i)b), by mono-hydroxylation with oxaziridines        of the Davis type and optionally subsequent etherification or    -   by aldol reaction with aldehydes of general formula

-   -   wherein R⁴ is as defined above, while excluding the hydroxy        group as the group R⁴.

The alkyation may be repeated with the same or a different alkylatingagent, so as to obtain □,□-disubstituted lactams of the compound(XXXIII). In the alkylation, mono-hydroxylation and the aldol reactionthe lactam of general formula (XXXV) may in each case be deprotonatedanalogously to the conditions described under (a)1)i)b) and reacted withan electrophil such as e.g. an oxaziridine (for examplephenylsulphonyloxaziridine or camphorsulphonyloxaziridine) or analdehyde of general formula (XXXVI).

-   5) Activation, nucleophilic substitution and reduction of the thus    introduced group of a compound of general formula

-   -   wherein A, X and R¹ to R⁵ are as defined above, and nucleophilic        substitution    -   with a compound selected for example from among lithium, sodium,        potassium azide, sodium, potassium phthalimide,        4-methoxybenzylamine, benzylamine, 2,4-dimethoxybenzylamine,        dibenzylamine, potassium or sodium cyanide,    -   and subsequent reduction of the nitrogen-containing group thus        introduced:    -   The activation of the alcohol function of a compound of        formula (XXV) is carried out using methods known from the        literature such as for example transformation into a chlorine,        bromine or iodine group or conversion into a nucleofugic group        such as for example mesylate, triflate or tosylate.

The nucleophilic substitution with a nitrogen nucleophil and thesubsequent reduction of the nitrogen nucleophil thus introduced iscarried out for example analogously to the method described in (f)3).

-   6) Reduction of the aliphatic nitro group of a compound of general    formula

-   -   wherein A, X, R¹ and R² are as defined above:

The reduction of the nitro group is conveniently carried out in asolvent or mixture of solvents such as for example methanol, ethanol,isopropanol, propanol, butanol, water in the presence of transitionmetal salts such as for example nickel(II)chloride or cobalt(II)chloridewith a reducing agent such as for example lithium borohydride, sodiumborohydride, for example at a temperature of −80° C. to 150° C., butpreferably between −20 and 100° C.

Compounds of general formula (XXXVII) may be prepared analogously to theconditions described in (c) by a tandem Michael addition/lactamisationfrom compounds of general formula (II) by reaction with for examplemethyl 3-nitro-but-3-enoate.

-   (g) In order to prepare a compound of general formula

-   -   wherein A, X, B and R¹ to R⁵ are as defined above:

-   1) Mitsunobu cyclodehydration of a compound of general formula

-   -   wherein A, X, B and R¹ to R⁵ are as defined above:

The lactamisation under Mitsunobu conditions is carried out for exampleanalogously to the method described in (e)3).

-   2) Acylation of a compound of general formula

-   -   wherein A, X and R¹ and R⁵ are as defined above, with a        carboxylic acid or a reactive carboxylic acid derivative of        general formula

-   -   wherein B is as defined above and Q denotes a hydroxy or        C₁₋₄-alkoxy group, a halogen atom or an acyloxy group.

The acylation is conveniently carried out with a corresponding halide oranhydride in a solvent such as methylene chloride, chloroform, carbontetrachloride, ether, tetrahydrofuran, dioxane, benzene, toluene,acetonitrile, dimethylformamide, sodium hydroxide solution orsulpholane, optionally in the presence of an inorganic or organic baseat temperatures between −20 and 200° C., but preferably at temperaturesbetween −10 and 160° C.

The acylation may however also be carried out with the free acid,optionally in the presence of an acid-activating agent or a dehydratingagent, for example in the presence of isobutyl chloroformate, thionylchloride, trimethylchlorosilane, hydrogen chloride, sulphuric acid,methanesulphonic acid, p-toluenesulphonic acid, phosphorus trichloride,phosphorus pentoxide, N,N′-dicyclohexylcarbodiimide,N,N′-dicyclohexylcarbodiimide/N-hydroxysuccinimide or1-hydroxy-benzotriazole, N,N′-carbonyldiimidazole,N,N′-carbonylditriazole,O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyl-uroniumtetrafluoroborate/N-methylmorpholine,O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyl-uroniumtetrafluoroborate/N-ethyldiisopropylamine,O-pentafluorophenyl-N,N,N′,N′-tetramethyluronium-hexafluoro-phosphate/triethylamine,N,N′-thionyldiimidazole or triphenylphosphine/carbon tetrachloride, attemperatures between −20 and 200° C., but preferably at temperaturesbetween −10 and 160° C.

Other methods of amide coupling are described for example in P. D.Bailey, I. D. Collier, K. M. Morgan in “Comprehensive Functional GroupInterconversions”, Vol. 5, page 257ff., Pergamon 1995.

In the reactions described hereinbefore any reactive groups present suchas hydroxy, carboxy, amino, alkylamino or imino groups may be protectedduring the reaction by conventional protective groups which are cleavedagain after the reaction.

For example a protecting group for a hydroxy group might be the methoxy,benzyloxy, trimethylsilyl, acetyl, benzoyl, tert.-butyl, trityl, benzylor tetrahydropyranyl group,

protecting groups for a carboxyl group might be the trimethylsilyl,methyl, ethyl, tert.-butyl, benzyl or tetrahydropyranyl group and

a protecting group for an amino, alkylamino or imino group might be theacetyl, trifluoroacetyl, benzoyl, ethoxycarbonyl, tert.-butoxycarbonyl,benzyloxycarbonyl, benzyl, methoxybenzyl or 2,4-dimethoxybenzyl groupand additionally, for the amino group, the phthalyl group.

Other protective groups and their removal are described in T. W. Greene,P. G. M. Wuts, “Protective Groups in Organic Synthesis”, Wiley, 1991 and1999.

Any protective group used is optionally subsequently cleaved for exampleby hydrolysis in an aqueous solvent, e.g. in water, isopropanol/water,tetrahydrofuran/water or dioxane/water, in the presence of an acid suchas trifluoroacetic acid, hydrochloric acid or sulphuric acid or in thepresence of an alkali metal base such as lithium hydroxide, sodiumhydroxide or potassium hydroxide or by means of ether splitting, e.g. inthe presence of iodotrimethylsilane, at temperatures between 0 and 100°C., preferably at temperatures between 10 and 50° C.

A benzyl, methoxybenzyl or benzyloxycarbonyl group, however, is cleavedby hydrogenolysis, for example, e.g. with hydrogen in the presence of acatalyst such as palladium/charcoal in a solvent such as methanol,ethanol, ethyl acetate, dimethylformamide, dimethylformamide/acetone orglacial acetic acid, optionally with the addition of an acid such ashydrochloric acid at temperatures between 0 and 50° C., but preferablyat ambient temperature, and under a hydrogen pressure of 1to 7 bar, butpreferably 1to 5 bar.

A methoxybenzyl group may also be cleaved in the presence of anoxidising agent such as cerium(IV)ammonium nitrate in a solvent such asmethylene chloride, acetonitrile or acetonitrile/water at temperaturesbetween 0 and 50° C., but preferably at ambient temperature.

A methoxy group is conveniently cleaved in the presence of borontribromide in a solvent such as methylene chloride at temperaturesbetween −35 and −25° C.

A 2,4-dimethoxybenzyl group, however, is preferably cleaved intrifluoroacetic acid in the presence of anisol.

A tert.-butyl or tert.-butyloxycarbonyl group is preferably cleaved bytreatment with an acid such as trifluoroacetic acid or hydrochloricacid, optionally using a solvent such as methylene chloride, dioxane orether.

A phthalyl group is preferably cleaved in the presence of hydrazine or aprimary amine such as methylamine, ethylamine or n-butylamine in asolvent such as methanol, ethanol, isopropanol, toluene/water or dioxaneat temperatures between 20 and 50° C.

An allyloxycarbonyl group is cleaved by treatment with a catalyticamount of tetrakis-(triphenylphosphine)-palladium(0), preferably in asolvent such as tetrahydrofuran and preferably in the presence of anexcess of a base such as morpholine or 1,3-dimedone at temperaturesbetween 0 and 100° C., preferably at ambient temperature and under inertgas, or by treatment with a catalytic amount oftris-(triphenylphosphine)-rhodium(I)chloride in a solvent such asaqueous ethanol and optionally in the presence of a base such as1,4-diazabicyclo[2.2.2]octane at temperatures between 20 and 70° C.

Moreover, the compounds of general formula I obtained may be resolvedinto their enantiomers and/or diastereomers.

Thus, for example, the compounds of general formula I obtained whichoccur as racemates may be separated by methods known per se (cf.Allinger N. L. and Eliel E. L. in “Topics in Stereochemistry”, Vol. 6,Wiley Interscience, 1971) into their optical enantiomers and compoundsof general formula I with at least 2 asymmetric carbon atoms may beresolved into their diastereomers on the basis of theirphysical-chemical differences using methods known per se, e.g. bychromatography and/or fractional crystallisation, and, if thesecompounds are obtained in racemic form, they may subsequently beresolved into the enantiomers as mentioned above.

The enantiomers are preferably separated by column separation on chiralphases or by recrystallisation from an optically active solvent or byreacting with an optically active substance which forms salts orderivatives such as e.g. esters or amides with the racemic compound,particularly acids and the activated derivatives or alcohols thereof,and separating the diastereomeric mixture of salts or derivatives thusobtained, e.g. on the basis of their differences in solubility, whilstthe free antipodes may be released from the pure diastereomeric salts orderivatives by the action of suitable agents. Optically active acids incommon use are e.g. the D- and L-forms of tartaric acid ordibenzoyltartaric acid, di-o-tolyltartaric acid, malic acid, mandelicacid, camphorsulphonic acid, glutamic acid, aspartic acid or quinicacid. An optically active alcohol may be, for example, (+) or(−)-menthol and an optically active acyl group in amides, for example,may be a (+)- or (−)-menthyloxycarbonyl.

Furthermore, the compounds of formula I may be converted into the saltsthereof, particularly for pharmaceutical use into the physiologicallyacceptable salts with inorganic or organic acids. Acids which may beused for this purpose include for example hydrochloric acid, hydrobromicacid, sulphuric acid, methanesulphonic acid, phosphoric acid, fumaricacid, succinic acid, lactic acid, citric acid, tartaric acid or maleicacid.

Moreover, if the new compounds of formula I contain a carboxy group,they may subsequently, if desired, be converted into the salts thereofwith inorganic or organic bases, particularly for pharmaceutical useinto the physiologically acceptable salts thereof. Suitable bases forthis purpose include for example sodium hydroxide, potassium hydroxide,cyclohexylamine, ethanolamine, diethanolamine and triethanolamine.

As already mentioned hereinbefore, the compounds of general formula Iand the tautomers, enantiomers, diastereomers and physiologicallyacceptable salts thereof have valuable pharmacological properties,particularly an antithrombotic activity which is preferably based on aneffect on thrombin or factor Xa, for example on a thrombin-inhibiting orfactor Xa-inhibiting activity, on a prolonging effect on the aPTT timeand/or on an inhibitory effect on related serine proteases such as e.g.urokinase, factor VIIa, factor IX, factor XI and factor XII.

The compounds listed in the Experimental Section were investigated fortheir effect on the inhibition of factor Xa as follows:

Method:

Enzyme-kinetic measurement with chromogenic substrate. The quantity ofp-nitroaniline (pNA) released from the colourless chromogenic substrateby human factor Xa is determined photometrically at 405 nm. It isproportional to the activity of the enzyme used. The inhibition of theenzyme activity by the test substance (in relation to the solventcontrol) is determined at various concentrations of test substance andfrom this the IC₅₀ is calculated, as the concentration which inhibitsthe factor Xa used by 50%.

Material:

Tris(hydroxymethyl)-aminomethane buffer (100 mMol) and sodium chloride(150 mMol), pH 8.0 plus 1mg/ml Human Albumin Fraction V, protease-free

Factor Xa (Calbiochem), spec. activity: 217 IU/mg, final concentration:7 IU/ml for each reaction mixture

Substrate S 2765 (Chromogenix), final concentration: 0.3 mM/l (1 KM) foreach reaction mixture

Test substance: final concentration 100, 30, 10, 3, 1, 0.3, 0.1, 0.03,0.01, 0.003, 0.001 μMol/l

Procedure:

10 μl of a 23.5-times concentrated starting solution of the testsubstance or solvent (control), 175 μl of TRIS/HSA buffer and 25 μl of a65.8 U/L Factor Xa working solution are incubated for 10 minutes at 37°C. After the addition of 25 μl of S 2765 working solution (2.82 mMol/l)the sample is measured in a photometer (SpectraMax 250) at 405 nm for600 seconds at 37° C.

Evaluation:

-   1. Determining the maximum increase (deltaOD/minutes) over 21    measuring points.-   2. Determining the % inhibition based on the solvent control.-   3. Plotting a dosage/activity curve (% inhibition vs substance    concentration).-   4. Determining the IC₅₀ by interpolating the X-value (substance    concentration) of the dosage/activity curve at Y=50% inhibition.

All the compounds tested had an IC₅₀ value of less than 100 μmol/L.

The compounds prepared according to the invention are generally welltolerated.

In view of their pharmacological properties the new compounds and thephysiologically acceptable salts thereof are suitable for the preventionand treatment of venous and arterial thrombotic diseases, such as forexample the prevention and treatment of deep leg vein thrombosis, forpreventing reocclusions after bypass operations or angioplasty (PT(C)A),and occlusion in peripheral arterial diseases, and for preventing andtreating pulmonary embolism, disseminated intravascular coagulation andsevere sepsis, for preventing and treating DVT in patients withexacerbated COPD, for treating ulcerative colitis, for preventing andtreating coronary thrombosis, for preventing stroke and the occlusion ofshunts. In addition, the compounds according to the invention aresuitable for antithrombotic support in thrombolytic treatment, such asfor example with alteplase, reteplase, tenecteplase, staphylokinase orstreptokinase, for preventing long-term restenosis after PT(C)A, for theprevention and treatment of ischaemic events in patients with all formsof coronary heart disease, for preventing metastasis and the growth oftumours and inflammatory processes, e.g. in the treatment of pulmonaryfibrosis, for preventing and treating rheumatoid arthritis, forpreventing and treating fibrin-dependent tissue adhesions and/or theformation of scar tissue and for promoting wound healing processes. Thenew compounds and the physiologically acceptable salts thereof may beused therapeutically in conjunction with acetylsalicylic acid, withinhibitors of platelet aggregation such as fibrinogen receptorantagonists (e.g. abciximab, eptifibatide, tirofiban, roxifiban), withphysiological activators and inhibitors of the clotting system and therecombinant analogues thereof (e.g. Protein C, TFPI, antithrombin), withinhibitors of ADP-induced aggregation (e.g. clopidogrel, ticlopidine),with P₂T receptor antagonists (e.g. cangrelor) or with combinedthromboxane receptor antagonists/synthetase inhibitors (e.g. terbogrel).

The dosage required to achieve such an effect is appropriately 0.01 to 3mg/kg, preferably 0.03 to 1.0 mg/kg by intravenous route, and 0.03 to 30mg/kg, preferably 0.1 to 10 mg/kg by oral route, in each caseadministered 1 to 4 times a day.

For this purpose, the compounds of formula I prepared according to theinvention may be formulated, optionally together with other activesubstances, with one or more inert conventional carriers and/ordiluents, e.g. with corn starch, lactose, glucose, microcrystallinecellulose, magnesium stearate, polyvinylpyrrolidone, citric acid,tartaric acid, water, water/ethanol, water/glycerol, water/sorbitol,water/polyethylene glycol, propylene glycol, cetylstearyl alcohol,carboxymethylcellulose or fatty substances such as hard fat or suitablemixtures thereof, to produce conventional galenic preparations such asplain or coated tablets, capsules, powders, suspensions orsuppositories.

The Examples that follow are intended to illustrate the invention,without restricting its scope:

Experimental Section

As a rule, melting points, IR, UV, ¹H-NMR and/or mass spectra have beenobtained for the compounds prepared. Unless otherwise stated, R_(f)values were determined using ready-made silica gel 60 F₂₅₄ TLC plates(E. Merck, Darmstadt, Item no. 1.05714) without chamber saturation. TheR_(f) values given under the heading Alox were determined usingready-made aluminium oxide 60 F₂₅₄ TLC plates (E. Merck, Darmstadt, Itemno. 1.05713) without chamber saturation. The R_(f) values given underthe heading Reversed-phase-8 (RP-8) were determined using ready-madeRP-8 F_(254s) TLC plates (E. Merck, Darmstadt, Item no. 1.15684) withoutchamber saturation. The ratios given for the eluants refer to units byvolume of the solvents in question. For chromatographic purificationsilica gel made by Messrs Millipore (MATREX™, 35-70 my) was used. Unlessmore detailed information is provided as to the configuration, it is notclear whether the products are pure stereoisomers or mixtures ofenantiomers and diastereomers.

The following abbreviations are used in the descriptions of theexperiments:

Boc tert.-butoxycarbonyl DCC N,N′-dicyclohexylcarbodiimide DIPEAN-ethyl-diisopropylamine DMSO dimethylsulphoxide DMFN,N-dimethylformamide DPPA diphenylphosphorylazide sat. saturated i.vac. in vacuo conc. concentrated NMM N-methyl-morpholine NMPN-methyl-pyrrolidin-2-one o ortho PfTUO-pentafluorophenyl-N,N,N′,N′-tetramethyluronium- hexafluorophosphatePPA propanephosphonic acid cycloanhydride quant. quantitative R_(f)retention factor R_(t) retention time rac. racemic TBTUO-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate TEAtriethylamine TFA trifluoroacetic acid THF tetrahydrofuran tert.tertiary Σ yield over all the steps described, carried out analogously

The HPLC data were obtained under the following conditions:

Waters ZMD, Alliance 2695 HPLC, Waters 2700 Autosampler, Waters 996

Diode array detector

The mobile phase used was:

A: water with 0.13% TFA

B: acetonitrile with 0.10% TFA

time in min % A % B flow rate in ml/min 0.0 95 5 1.00 0.7 95 5 1.00 5.22 98 1.00 5.7 2 98 1.00 6.0 95 5 1.00 6.5 95 5 1.00

The stationary phase used was a Varian column, Microsorb 100 C₁₈ 3 μm,4.6 mm×50 mm, batch no. 2231108 (column temperature: constant at 25°C.).

The diode array detection was carried out at a wavelength range of210-300 nm.

EXAMPLE 1 5-bromo-thiophene-2-carboxylicacid-{1-[3-chloro-4-(2-oxo-[1,3]oxazinan-3-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide

(a) 3-chloropropyl (2-chloro-4-nitro-phenyl)-carbamate

2.0 g (11.59 mmol) 2-chloro-4-nitro-aniline are suspended in 10 ml oftoluene and refluxed for two hours with the addition of 1.41 ml (11.59mmol) diphosgene. Then the mixture is evaporated to dryness in vacuo.The crude product thus obtained is suspended in 50 ml of toluene andcombined with 0.97 ml (11.59 mmol) 3-chloro-propan-1-ol. The mixture isstirred for three hours at 60° C. and the mixture is then evaporated todryness. The residue is purified by chromatography on silica gel(petroleum ether/ethyl acetate 98:2).

Yield: 38% R_(f) value: 0.22 (silica gel, petroleum ether/ethyl acetate9:1) C₁₀H₁₀Cl₂N₂O₄ (293.10) Mass spectrum: (M+H)⁺=291/293/295 (chlorineisotopes)

(b) 3-(2-chloro-4-nitro-phenyl)-[1,3]oxazinan-2-one

1.2 g (4.1 mmol) 3-chloropropyl (2-chloro-4-nitro-phenyl)-carbamate aredissolved in 36 ml acetonitrile, combined with 960 mg (6.9 mmol)potassium carbonate and refluxed for 1.5 hours. The reaction mixture iscooled to ambient temperature, filtered to remove undissolved matter andthe filtrate is evaporated to dryness.

Yield: quantitative R_(f) value: 0.17 (silica gel, petroleum ether/ethylacetate 1:1) C₁₀H₉ClN₂O₄ (256.64) Mass spectrum: (M+H)⁺=257/259(chlorine isotopes)

(c) 3-(4-amino-2-chloro-phenyl)-[1,3]oxazinan-2-one

200 mg (0.78 mmol) of 3-(2-chloro-4-nitro-phenyl)-[1,3]oxazinan-2-oneare dissolved in 10 ml of tetrahydrofuran and combined with 135 mg Raneynickel. The mixture is hydrogenated in a Parr apparatus at ambienttemperature at 1 atm hydrogen pressure for three hours. Then the Raneynickel is filtered off and the filtrate is evaporated down i. vac.Yield: 150 mg (85%)

R_(f) value: 0.16 (silica gel; petroleum ether/ethyl acetate 1:1)C₁₀H₁₁ClN₂O₂ (226.66) Mass spectrum: (M+H)⁺=227/229 (chlorine isotopes)

(d)1-[3-chloro-4-(2-oxo-[1,3]oxazinan-3-yl)-phenyl]-5-oxo-pyrrolidine-3-carboxylicacid

670 mg (2.96 mmol) 3-(4-amino-2-chloro-phenyl)-[1,3]oxazinan-2-one and385 mg (2.96 mmol) itaconic acid are melted together under an argonatmosphere at 150° C. for one hour. The mixture is allowed to cool andthe crude product is purified by trituration in dichloromethane.

Yield: 356 mg (36%) R_(f) value: 0.27 (silica gel;dichloromethane/methanol 9:1) C₁₀H₁₁ClN₂O₂ (338.74) Mass spectrum:(M+H)⁺=339/341 (chlorine isotopes)

(e) tert. butyl {1-[3-chloro-4-(2-oxo-[13]oxazinan-2-on-3-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-carbamate

260 mg (0.77 mmol)1-[3-chloro-4-(2-oxo-[1,3]oxazinan-3-yl)-phenyl]-5-oxo-pyrrolidine-3-carboxylicacid are suspended in 5 ml tert.-butanol and combined with 106 μl (0.77mmol) triethylamine at ambient temperature. After 15 min stirring 170 μl(0.77 mmol) DPPA are added and the mixture is refluxed for 5 hours. Itis left to cool and the volatile constituents are eliminated using therotary evaporator. The solid residue is purified by chromatography onsilica gel (eluant-gradient: dichloromethane/isopropanol 97:3 to 95:5).

Yield: 154 mg (49%) R_(t) value: 2.63 min C₁₉H₂₄ClN₃O₅ (409.86) Massspectrum: (M+H)⁺=410/412 (chlorine isotopes)

(f)3-[4-(4-amino-2-oxo-pyrrolidin-1-yl)-2-chloro-phenyl]-[1,3]oxazinan-2-one-trifluoroacetate

40 mg (98pmol) tert. butyl{1-[3-chloro-4-(2-oxo-[1,3]oxazinan-2-on-3-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-carbamateare dissolved in 3 ml dichloromethane, combined with 70 μltrifluoroacetic acid and stirred for 16 hours at ambient temperature.The mixture is evaporated to dryness and combined again withdichloromethane and trifluoroacetic acid. After one hour it isevaporated to dryness.

Yield: quantitative R_(t) value: 2.63 min C₁₄H₁₆ClN₃O₃ (309.75) Massspectrum: (M+H)⁺=310/312 (chlorine isotopes)

(g) 5-bromo-thiophene-2-carboxylicacid-{1-[3-chloro-4-(2-oxo-[1,3]oxazinan-3-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide

21 mg (100 μmol) 5-bromo-thiophene-2-carboxylic acid are combined in 3ml DMF with 66 μl (100 μmol) NMM and 32 mg (74 μmol) TBTU and thenstirred for 10 min under a nitrogen atmosphere at ambient temperature.Then 42 mg (99 μmol)3-[4-(4-amino-2-oxo-pyrrolidin-1-yl)-2-chloro-phenyl]-[1,3]oxazinan-2-one-trifluoroacetatedissolved in 1 ml DMF are added and the mixture is stirred for two hoursat ambient temperature. Then the reaction mixture is combined with sat.sodium hydrogen carbonate solution and water and extracted with ethylacetate. The aqueous phase is extracted twice with ethyl acetate. Thecombined organic phases are dried over sodium sulphate and totallyevaporated down i. vac. The residue is chromatographed on silica gel(eluant: dichloromethane/ethanol 95:5).

Yield: 24 mg (49%) R_(f) value: 0.09 (silica gel;dichloromethane/ethanol 95:5) C₁₉H₁₇BrClN₃O₄S (498.78) Mass spectrum:(M+H)⁺=498/500/502 (bromine/chlorine isotopes)

The following compounds were prepared analogously:

No. Structural formula Yield Mass peak(s) R_(f) value or R_(t) Name 3

Σ: 17.3% (M − H)⁻= 432/434 (chlorine isotopes) 0.17 (silica gel,dichloromethane /isopropanol = 95:5) 5-chloro-thiophene-2-carboxylicacid-N-{1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide 4

Σ: 21.0% (M + H)⁺= 478/480 (bromine isotope) 0.17 (silica gel,dichloromethane /isopropanol = 95:5) 5-bromo-thiophene-2-carboxylicacid-N-{1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide 5

Σ: 14.5% (M + H)⁺= 429/431 (chlorine isotopes) 0.20 (silica gel,dichloromethane /isopropanol = 95:5) 5-chloro-pyridine-2-carboxylicacid-{1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide 6

Σ: 15.7% (M − H)⁻= 412 0.20 (silica gel, dichloromethane /isopropanol =95:5) 5-methyl-thiophene-2-carboxylicacid-{1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide 7

Σ: 14.3% (M + H)⁺= 479/481 (bromine isotope) 0.20 (silica gel,dichloromethane /isopropanol = 95:5) 5-bromo-thiazole-2-carboxylicacid-{1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide 8

Σ: 2.5% (M + H)⁺= 454/456/458 (chlorine isotopes) 0.09 (silica gel,dichloromethane /ethanol = 95:5) 5-chloro-thiophene-2-carboxylicacid-{1-[3-chloro-4-(2-oxo-[1,3]oxazinan-3-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide 17

Σ: 1.0% (M + H)⁺= 499/501/503 (bromine, chlorine isotopes) 4.05 min2-bromo-thiazole-5-carboxylicacid-{1-[3-chloro-4-(2-oxo-[1,3]-oxazinan-3-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide 20

Σ: 0.2% (M + H)⁺= 492/494 (bromine isotope) 4.19 min5-bromo-thiophene-2-carboxylic acid-{1-[3-methyl-4-(5-oxo-[1,4]oxazepan-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide 22

Σ: 0.2% (M + H)⁺= 438 2.54 min 5-ethynyl-thiophene-2-carboxylicacid-{1-[3-methyl-4-(5-oxo-[1,4]oxazepan-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide 44

Σ: 0.7% (M + H)⁺= 511/513/515 (bromine, chlorine isotopes) 2.51 min5-bromo-thiophene-2-carboxylic acid-{1-[3-chloro-4-(4-methyl-[1,4]diazepam-1-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide 45

Σ: 1.9% (M − H)⁻= 450/452/454 (chlorine isotopes) 0.63 (silica gel,dichloromethane /methanol/ conc. ammonia 90:10:1)5-chloro-thiophene-2-carboxylicacid-[1-(4-azepan-1-yl-3-chloro-phenyl]-5- oxo-pyrrolidin-3-yl}-amide 46

Σ: 4.7% (M − H)⁻= 440/442 (chlorine isotopes) 0.55 (silica gel,dichloromethane /methanol/ conc. ammonia 90:10:1)5-ethynyl-thiophene-2-carboxylic acid-{1-[3-methyl-4-(5-oxo-[1,4]oxazepan-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide 47

Σ: 3.6% (M + H)⁺= 456/458 (chlorine isotopes) 0.44 (silica gel,dichloromethane /methanol/ conc. ammonia 90:10:1)5-ethynyl-thiophene-2-carboxylic acid-{1-[3-chloro-4-(2-oxo-azepan-1-yl)- phenyl]-5-oxo-pyrrolidin-3-yl}-amide 48

Σ: 2.3% (M − H)⁻= 464/466 (chlorine isotopes) 0.45 (silica gel,dichloromethane /methanol/ conc. ammonia 90:10:1)5-chloro-thiophene-2-carboxylic acid-{1-[3-chloro-4-(2-oxo-azepan-1-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide 68

Σ: 6.6% (M − H)⁻= 537/539/541 (chlorine isotopes) 0.32 (silica gel,dichloromethane /mehtanol 20:1) tert. butyl4-(2-chloro-4-{4-[5-chloro-thiophene-2-carbonyl)-amino]-2-oxo-pyrrolidin-1-yl}-phenyl)-piperazine-1-carboxylate 69

Σ: 17% (M + H)⁺= 583/585/587 (bromine, chlorine isotopes) 0.45 (silicagel, dichloromethane /methanol 15:1) tert. butyl4-(2-chloro-4-{4-[5-bromo-thiophene-2-carbonyl)-amino]-2-oxo-pyrrolidin-1-yl}-phenyl)-piperazine-1-carboxylate 70

Σ: 5.7% (M + H)⁺= 439/441/443 (chlorine isotopes) 0.76 (silica gel,dichloromethane /methanol/conc. ammonia (.2:0.1)5-chloro-thiophene-2-carboxylicacid-[1-(3-chloro-4-piperazin-1-yl-phenyl)- 5-oxo-pyrrolidin-3-yl]-amide(as the hydrochloride salt) 71

Σ: 7.0% (M + H)⁺= 483/485/487 (bromine, chlorine isotopes) 0.76 (silicagel, dichloromethane /methanol/conc. ammonia (.2:0.1)5-bromo-thiophene-2-carboxylicacid-[1-(3-chloro-4-piperazin-1-yl-phenyl)- 5-oxo-pyrrolidin-3-yl]-amide(as the hydrochloride salt) 72

Σ: 0.7% (M + H)⁺= 537/539/541 (chlorine isotopes) 0.35 (silica gel,dichloromethane /methanol/ conc. ammonia 90:10:1)5-chloro-thiophene-2-carboxylic acid-(1-{3-chloro-4-[2-(2-diethylamino-ethyl)-piperidin-1-yl]-phenyl}-5-oxo-pyrrolidin-3-yl)-amide (as thetrifluoroacetate salt) 73

Σ: 6.7% (M − H)⁻= 494/496/498 (bromine, chlorine isotopes) 0.32 (silicagel, dichloromethane /methanol 15:1) 5-bromo-thiophene-2-carboxylicacid-[1-(4-azepan-1-yl-3-chloro-phenyl)-5- oxo-pyrrolidin-3-yl]-amide 74

Σ: 2.4% (M − H)⁻= 452/454/456 (chlorine isotopes) 0.32 (silica gel,dichloromethane /methanol 15:1) 5-chloro-thiophene-2-carboxylicacid-[1-(3-chloro-4-[1,4]oxazepan-4-yl-phenyl)-5-oxo-pyrrolidin-3-yl]-amide 75

Σ: 2.2% (M − H)⁻= 496/498/500 (bromine, chlorine isotopes) 0.22 (silicagel, dichloromethane /methanol 15:1) 5-bromo-thiophene-2-carboxylicacid-[1-(3-chloro-4-[1,4]oxazepan-4-yl-phenyl)-5-oxo-pyrrolidin-3-yl]-amide 76

Σ: 0.6% (M + H)⁺= 453/455 (chlorine isotopes) 0.17 (silica gel,dichloromethane /methanol/ conc. ammonia 90:10:1)5-chloro-thiophene-2-carboxylic acid-[1-(3-chloro-4-[1,4]diazepan-1-yl-phenyl)-5-oxo-pyrrolidin-3-yl]-amide (as the hydrochloride salt) 77

Σ: 4.3% (M + H)⁺= 537/539/541 (chlorine isotopes) 0.57 (silica gel,dichloromethane /methanol 15:1)1-(2-chloro-4-{4-[5-chloro-thiophene-2-carbonyl)-amino]-2-oxo-pyrrolidin-1-yl}-phenyl)-piperidin-3-carboxylic acid diethylamide 78

Σ: 3.3% (M + H)⁺= 581/583/585 (bromine, chlorine isotopes) 0.56 (silicagel, dichloromethane /methanol 9:1) 5-bromo-thiophene-2-carboxylicacid-[1-(3-chloro-4-[1,4]oxazepan-4-yl-phenyl)-5-oxo-pyrrolidin-3-yl]-amide 79

Σ: 0.4% (M + H)⁺= 497/499/501 (bromine, chlorine isotopes) 0.17 (silicagel, dichloromethane /methanol/ conc. ammonia 90:10:1)5-bromo-thiophene-2-carboxylic acid-[1-(3-chloro-4-[1,4]diazepan-1-yl-phenyl)-5-oxo-pyrrolidin-3-yl]-amide (as the trifluoroacetate salt)

EXAMPLE 2 (R)-5-bromo-thiophene-2-carboxylicacid-{1-[2-fluoro-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide

(a) 4-(4-amino-3-fluoro-phenyl)-morpholin-3-one

2.0 g (8.4 mmol) 2-fluoro-4-iodo-aniline, 860 mg (8.5 mmol)morpholin-3-one, 162 mg (0.86 mmol) copper(I)iodide, 2.33 g (16.86 mmol)potassium carbonate and 91 μl N,N′-dimethylethylenediamine are suspendedin 18 ml of toluene under an argon atmosphere and stirred for two hoursin a microwave at a power of 35 Watts at 140° C. Water is added and themixture is extracted three times with ethyl acetate. The combinedorganic phases are dried over sodium sulphate and evaporated to dryness.The residue is purified by chromatography on silica gel (eluant:dichloromethane/methanol 50:1).

Yield: 590 mg (33%) R_(f) value: 0.60 (silica gel;dichloromethane/methanol 9:1) C₁₀H₁₁FN₂O₂ (210.21) Mass spectrum:(M+H)⁺=211

(b) benzyl(2-hydroxy-(1R)-1-{[2-fluoro-4-(3-oxo-morpholin-4-yl)-phenylcarbamoyl]-methyl}-ethyl)-carbamate

490 mg (2.3 mmol) 4-(4-amino-2-fluoro-phenyl)-morpholin-3-one aredissolved in 3 ml dichloromethane and at ambient temperature slowlycombined with 1.18 ml of a solution of trimethylaluminium in toluene(2M, 2.35 mmol). The mixture is stirred for 15 min and then 554 mg (2.3mmol) benzyl (R)-(5-oxo-tetrahydrofuran-3-yl)-carbamate are added andstirring is continued for 16 hours at ambient temperature. Subsequentlythe mixture is acidified with 2.5 ml of 2N hydrochloric acid, dilutedwith water and extracted three times with ethyl acetate. The combinedorganic phases are dried over sodium sulphate and evaporated to dryness.The crude product thus obtained is purified by chromatography on silicagel (eluant: dichloromethane/methanol 20:1).

Yield: 310 mg (30%) R_(f) value: 0.60 (silica gel;dichloromethane/methanol 9:1) C₂₂H₂₄FN₃O₆ (445.44) Mass spectrum:(M+H)⁺=446

(c) benzyl(R)-{1-[2-fluoro-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-carbamate

310 mg (0.7 mmol) benzyl(2-hydroxy-(1R)-1-{[2-fluoro-4-(3-oxo-morpholin-4-yl)-phenylcarbamoyl]-methyl}-ethyl)-carbamateare dissolved in 3.5 ml THF. While cooling with ice a mixture of 205 mg(0.89 mmol) di-tert.-butyl azodicarboxylate and 210 μl (0.83 mmol)tributylphosphine in 6 ml THF is added. The mixture is slowly heated toambient temperature and stirred for 16 hours. The mixture is thenevaporated to dryness. The residue is purified by reversed-phasechromatography.

Yield: 210 mg (71%) R_(t) value: 2.59 min C₂₃H₂₅N₃O₅ (427.23) Massspectrum: (M+H)⁺=428

(d)(R)-4-[4-(4-amino-2-oxo-pyrrolidin-1-yl)-3-fluoro-phenyl]-morpholin-3-one

260 mg (0.6 mmol) benzyl(R)-{1-[2-fluoro-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-carbamateare dissolved in 10 ml of methanol, combined with 180 mg palladium oncharcoal and hydrogenated for 3.75 hours in a Parr apparatus at 3 barhydrogen pressure at ambient temperature.

The mixture is filtered to remove the catalyst and evaporated to drynessusing the rotary evaporator.

Yield: 124 mg (70%) R_(f) value: 0.15 (silica gel;dichloromethane/methanol 95:5) C₁₅H₁₉N₃O₃ (293.29) Mass spectrum:(M+H)⁺=294

(e) (R)-5-bromo-thiophene-2-carboxylicacid-{1-[2-fluoro-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide

Prepared analogously to Example 1g from 5-bromo-thiophene-2-carboxylicacid and(R)-4-[4-(4-amino-2-oxo-pyrrolidin-1-yl)-3-fluoro-phenyl]-morpholin-3-onewith TBTU and NMM in DMF and subsequent purification by reversed-phasechromatography.

Yield: 42% R_(f) value: 0.54 (silica gel; dichloromethane/methanol 95:5)C₁₉H₁₇BrFN₃O₄S (482.33) Mass spectrum: (M+H)⁺=482/484 (bromine isotope)

The following compounds were prepared analogously:

No. Structural formula Yield Mass peak(s) R_(f) value or R_(t) Name 9

Σ: 8.1% (M +H)^(+ = 478/480 (bromine isotope)) 2.70 min(R)-5-bromo-thiophene-2-carboxylic acid-{1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide 10

Σ: 0.4% (M −H)^(− = 463/465 (bromine isotope)) 0.06 (silica gel,dichloromethane/ ethanol 95:5) (R)-5-bromo-thiophene-2-carboxylicacid-{5-oxo-1-[5-(3-oxo-morpholin-4-yl)-pyridin-2-yl]-pyrrolidin-3-yl}-amide 11

Σ: 12.2% (M +H)^(+ = 478/480 (bromine isotope)) 2.63 min(S)-5-bromo-thiophene-2-carboxylic acid-{1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide 12

Σ: 2.0% (M +H)^(+ = 438/440 (bromine isotope)) 0.51 (silica gel,dichloromethane/ methanol = 95:5) (R)-5-chloro-thiophene-2-carboxylicacid-{1-[2-fluoro-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide 19

Σ: 5.2% (M +H)^(+ = 500/502 (bromine isotope)) 2.73 min(R)-5-bromo-thiophene-2-carboxylic acid-{1-[2.5-difluoro-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide 21

Σ: 1.7% (M +H)⁺ ⁼ ⁴²⁴ 2.58 min (R)-5-ethynyl-thiophene-2-carboxylicacid-{1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide 33

Σ: 4.3% (M +H)^(+ = 462/464 (bromine isotope)) 2.75 min(R)-5-bromo-thiophene-2-carboxylicacid-{5-oxo-1-[4-(2-oxo-piperidin-1-yl)- phenyl]-pyrrolidin-3-yl}-amide34

Σ: 5.9% (M −H)⁻ ⁼ ⁴⁰⁶ 2.63 min (R)-5-ethynyl-thiophene-2-carboxylicacid-{5-oxo-1-[4-(2-oxo-piperidin-1- yl)-phenyl]-pyrrolidin-3-yl}-amide35

Σ: 2.8% (M −H)⁻ ⁼ ⁴⁷⁶ 2.78 min (R)-5-ethynyl-thiophene-2-carboxylicacid-{5-oxo-1-[4-(3-oxo-morpholin-4-yl)-3-trifluoromethyl-phenyl]-pyrrolidin-3-yl}-amide 36

Σ: 6.1% (M +H)^(+ = 532/354 (bromine isotope)) 2.88 min(R)-5-bromo-thiophene-2-carboxylic acid-{5-oxo-1-[4-(3-oxo-morpholin-4-yl)-3-trifluoromethyl-phenyl]-pyrrolidin-3-yL}-amide 37

Σ: 5.5% (M −H)^(− = 486/488 (chlorine isotopes)) 2.85 min(R)-5-chloro-thiophene-2-carboxylic acid-{5-oxo-1-[4-(3-oxo-morpholin-4-yl)-3-trifluoromethyl-phenyl]-pyrrolidin-3-yl}-amide 41

Σ: 0.03% (M +H)^(+ = 497/499/501 (bromine/chlorine isotopes)) 2.71 min(R)-5-bromo-thiophene-2-carboxylicacid-{1-[3-chloro-4-(2-oxo-tetrahydro-pyrimidin-1-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide 50

Σ: 2.7% (M +NH₄)^(+ = 509/511 (bromine isotopes)) 2.82 min(R)-5-bromo-thiophene-2-carboxylic acid-{1-[3-methyl-4-(2-oxo-[1,3]oxazepan-3-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide 51

Σ: 14.2% (M +H)^(+ = 498/500 (bromine isotopes)) 2.89 min(R)-5-bromo-thiophene-2-carboxylic acid-{1-[4-(1[-dioxo-1□⁶-isothiazolidin-2-yl)-3-methyl-phenyl]-5-oxo-pyrrolidin-3-yl}-amide 53

Σ: 2.9% (M +H)^(+ = 462/464 (bromine isotopes)) 2.75 min(R)-5-bromo-thiophene-2-carboxylicacid-{1-[3-methyl-4-(2-oxo-pyrrolidin-1-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide 54

Σ: 3.3% (M +H)^(+ = 418/420 (chlorine isotopes)) 2.71 min(R)-5-chloro-thiophene-2-carboxylicacid-{1-[3-methyl-4-(2-oxo-pyrrolidin-1-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide 55

Σ: 3.9% (M +H)⁺ ⁼ ⁴⁰⁸ 2.62 min (R)-5-ethynyl-thiophene-2-carboxylicacid-{1-[3-chloro-4-(2-oxo-tetrahydro-pyrimidin-1-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide 56

Σ: 1.1% (M +H)^(+ = 492/494 (bromine isotopes)) 2.75 min(R)-5-bromo-thiophene-2-carboxylicacid-{1-[3-methoxy-4-(2-oxo-piperidin-1-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide 57

Σ: 1.0% (M +H)^(+ = 448/450 (chlorine isotope)) 2.72 min(R)-5-chloro-thiophene-2-carboxylicacid-{1-[3-methoxy-4-(2-oxo-piperidin-1-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide 66

Σ: 13.8% (M +NH₄)^(+ = 455/457 (chlorine isotopes)) 2.63 min(R)-5-chloro-thiophene-2-carboxylicacid-{1-[3-fluoro-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide

EXAMPLE 13 5-bromo-thiophene-2-carboxylicacid-{1-[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide

(a) 1-(3-fluoro-4-nitro-phenyl)-1H-pyridin-2-one

2.5 g (26.3 mmol) 2-hydroxypyridine, 2.9 ml (26.3 mmol)2,4-difluoronitrobenzene, are dissolved in 100 ml acetone, combined with4.0 g (28.9 mmol) potassium carbonate and stirred for one day at ambienttemperature. The undissolved matter is filtered off and the saltresidues are rinsed with acetone. The combined organic phases areevaporated to dryness. The residue is purified by chromatography (silicagel; eluant: cyclohexane-ethyl acetate gradient).

Yield: 1.3 g (21%) R_(t) value: 3.67 min (K value: 4.650) C₁₁H₇FN₂O₃(234.18) Mass spectrum: (M+H)⁺=235

(b) 1-(4-amino-3-fluoro-phenyl)-1H-pyridin-2-one

1.8 g (7.7 mmol) 1-(3-fluoro-4-nitro-phenyl)-1H-pyridin-2-one aredissolved in 360 ml of ethanol, combined with 8.7 g (38.4 mmol)tin(II)chloride-hydrate and refluxed for 45 min. The mixture is cooledand concentrated to dryness. The residue is combined with equal amountsof 1N sodium hydroxide solution and ethyl acetate. The precipitate isfiltered off, water is added to the filtrate, the organic phase isseparated off and the aqueous phase is extracted twice with ethylacetate. The combined organic phases are dried over sodium sulphate andevaporated to dryness.

Yield: quantitative R_(t) value: 3.03 min (K value: 3.655) C₁₁H₉FN₂O(204.20) Mass spectrum: (M+H)⁺=205

(c)1-[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenyl]-5-oxo-pyrrolidine-3-carboxylicacid

Prepared analogously to Example 1d from1-(4-amino-3-fluoro-phenyl)-1H-pyridin-2-one by melting with itaconicacid. The crude product is purified by reversed-phase chromatography.

Yield: 22% R_(t) value: 2.89 min C₁₆H₁₃FN₂O₄ (316.28) Mass spectrum:(M+H)⁺=317

(d) tert. butyl{-[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-carbamate

Prepared analogously to Example 1e from1-[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenyl]-5-oxo-pyrrolidine-3-carboxylicacid by carboxylic acid breakdown by means of DPPA, tert.-butanol andtriethylamine.

Yield: 19% R_(t) value: 3.91 min (K value: 5.011) C₂₀H₂₂FN₃O₄ (387.41)Mass spectrum: (M+H)⁺=388

(e)1-[4-amino-2-oxo-pyrrolidin-1-yl)-3-fluoro-phenyl]-1H-pyridin-2-one-hydrochloride

154 mg (0.4 mmol) tert. butyl{1-[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-carbamateare suspended in 5 ml hydrochloric acid solution in dioxane (4-molar)and stirred for 45 minutes at ambient temperature. Then a further 5 mlhydrochloric acid solution in dioxane are added and the mixture isstirred for another two hours.

The suspension is evaporated to dryness.

Yield: quantitative R_(t) value: 2.76 min (K value: 3.247) C₁₅H₁₄FN₃O₂(287.30) Mass spectrum: (M+H)⁺=288

(f) 5-bromo-thiophene-2-carboxylicacid-{1-[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide

Prepared analogously to Example 1g from 5-bromo-thiophene-2-carboxylicacid and1-[4-amino-2-oxo-pyrrolidin-1-yl)-3-fluoro-phenyl]-1H-pyridin-2-one-hydrochloridewith TBTU and NMM in DMF and subsequent purification by reversed-phasechromatography.

Yield: 35% R_(t) value: 4.12 min (K value: 5.337) C₂₀H₁₅BrFN₃O₃S(476.32) Mass spectrum: (M+H)⁺=476/478 (bromine isotope)

The following compound was prepared analogously:

No. Structural formula Yield Mass peak(s) R_(f) value or R_(t) Name 14

Σ: 0.5% (M + H)^(+ = 432/434 (chlorine isotopes)) 4.05 min5-chloro-thiophene-2-carboxylicacid-{1-[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide

EXAMPLE 18 5-bromo-thiophene-2-carboxylicacid-{(3R,4R)-4-methyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide

(a) Benzyl [(3R,4R)-4-methyl-5-oxo-tetrahydrofuran-3-yl]-carbamate

272 μl (1.9 mmol) diisopropylamine are placed in 3 ml THF and whilecooling with ice 1.2 ml (1.9 mmol) of an n-butyllithium solution inhexane (1.6M) are added. The mixture is stirred for 10 minutes at 0° C.,then cooled to −78° C. and a solution of 200 mg (0.85 mmol) benzyl(R)-(5-oxo-tetrahydrofuran-3-yl)-carbamate in 1 ml THF is addeddropwise. The mixture is stirred for one hour at −78° C. Then 210 μl(3.3 mmol) methyl iodide are added dropwise, and the mixture is heatedto −60° C. within one hour. Then 0.5 ml sat. ammonium chloride solutionis added and the mixture is heated to ambient temperature. Water isadded and the mixture is extracted three times with ethyl acetate. Thecombined organic phases are dried over sodium sulphate and evaporated todryness. The residue is taken up in DMF, acidified with TFA and purifiedby reversed-phase chromatography.

Yield: 78 mg (37%) R_(t) value: 2.73 min C₁₃H₁₅NO₄ (249.26) Massspectrum: (M−H)⁻=248

(b) benzyl{(1R,2R)-1-hydroxymethyl-2-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenylcarbamoyl]-propyl}-carbamate

Prepared analogously to Example 2b from4-(4-amino-2-methyl-phenyl)-morpholin-3-one and benzyl[(3R,4R)-4-methyl-5-oxo-tetrahydrofuran-3-yl]-carbamate withtrimethylaluminium in THF and subsequent purification by reversed-phasechromatography.

Yield: 40% R_(t) value: 2.48 min C₂₄H₂₉N₃O₆ (455.50) Mass spectrum:(M+H)⁺=456

(c) benzyl{(3R,4R)-4-methyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-carbamate

Prepared analogously to Example 2c from benzyl{(1R,2R)-1-hydroxymethyl-2-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenylcarbamoyl]-propyl}-carbamatewith di-tert.-butyl azodicarboxylate and tributylphosphine in THF andsubsequent purification by reversed-phase chromatography.

Yield: 57% R_(t) value: 2.74 min C₂₄H₂₇N₃O₅ (437.39) Mass spectrum:(M+H)⁺=438

(d)4-{4-[(3R,4R)-4-amino-3-methyl-2-oxo-pyrrolidin-1-yl]-2-methyl-phenyl}-morpholin-3-one

Prepared analogously to Example 2d from benzyl{(3R,4R)-4-methyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-carbamateand subsequent purification by chromatography on silica gel.

Yield: 98% R_(f) value: 0.05 (silica gel; dichloromethane/methanol 95:5)C₁₆H₂₁N₃O₃ (303.36) Mass spectrum: (M+H)⁺=304

(e) 5-bromo-thiophene-2-carboxylicacid-{(3R,4R)-4-methyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide

Prepared analogously to Example 1d from 5-bromo-thiophene-2-carboxylicacid and4-{4-[(3R,4R)-4-amino-3-methyl-2-oxo-pyrrolidin-1-yl]-2-methyl-phenyl}-morpholin-3-onewith TBTU and NMM in DMF and subsequent purification by reversed-phasechromatography.

Yield: 31% R_(t) value: 2.83 min C₂₁H₂₂BrN₃O₄S (492.39) Mass spectrum:(M+H)⁺=492/494 (bromine isotope)

The following compounds were prepared analogously:

No. Structural formula Yield Mass peak(s) R_(f) value or R_(t) uz,4/7Name 25

Σ: 2.6% (M + H)⁺ = 438 2.67 min 5-ethynyl-thiophene-2-carboxylicacid-{(3R, 4R)-4-methyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide 52

Σ: 0.7% (M + H)⁺ = 520/522 (bromine isotopes) 3.03 min5-bromo-thiophene-2-carboxylic acid-{(3R, 4R)-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-4-propyl-pyrrolidin-3-yl}-amide 58

Σ: 1.0% (M + H)⁺ = 522/524 (bromine isotopes) 2.76 min5-bromo-thiophene-2-carboxylic acid-{(3R, 4R)-4-methoxymethyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide 59

Σ: 4.0% (M + H)⁺ = 524/526 (chlorine isotopes) 3.13 min5-chloro-thiophene-2-carboxylic acid-{(3R,4R)-4-benzyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide 60

Σ: 4.0% (M + H)⁺ = 568/570 (bromine isotopes) 3.13 min5-bromo-thiophene-2-carboxylic acid-{(3R, 4R)-4-benzyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide 61

Σ: 3.4% (M + H)⁺ = 514 3.01 min 5-ethynyl-thiophene-2-carboxylicacid-{(3R, 4R)-4-benzyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide 62

Σ: 0.5% (M − H)⁻ = 462/464 (chlorine isotopes) 2.68 min5-chloro-thiophene-2-carboxylic acid-{(3R, 4R)-4-methoxymethyl-5-oxo-1-[4-(3-oxo-morpholin-4-yl)-phenyl]-pyrrolidin-3-yl}-amide 63

Σ: 0.8% (M − H)⁻ = 472/474 (chlorine isotopes) 2.79 min5-chloro-thiophene-2-carboxylic acid-{(3R,4R)-4-allyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide 64

Σ: 0.8% (M + H)⁺ = 518/520 (bromine isotopes) 2.94 min5-bromo-thiophene-2-carboxylic acid-{(3R,4R)-4-allyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide 67

Σ: 0.8% (M + NH₄)⁺ = 495/497 (chlorine isotopes) 2.68 min5-chloro-thiophene-2-carboxylic acid-{(3R, 4R)-4-methoxymethyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide

EXAMPLE 24 5-bromo-thiophene-2-carboxylicacid-{1-[3-methyl-4-(2-oxo-[1,3]oxazepan-3-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide

(a) 4-chlorobutyl (2-methyl-4-nitro-phenyl)-carbamate

Prepared from 2-methyl-4-nitroaniline and diphosgene and subsequentreaction with 4-chloro-butan-1-ol analogously to Example1a andsubsequent recrystallisation from cyclohexane.

Yield: 68% R_(t) value: 5.21 min C₁₂H₁₅ClN₂O₄ (286.71) Mass spectrum:(M+H)⁺=285/287 (chlorine isotopes)

(b) 3-(2-methyl-4-nitro-phenyl)-[1,3]oxazepan-2-one

20.2 g (63.4 mmol) 4-chlorobutyl (2-methyl-4-nitro-phenyl)-carbamate aredissolved in 500 ml DMF and added to a suspension of 7.8 g (69.8 mmol)potassium-tert.-butoxide in 500 ml DMF. The reaction solution is stirredfor four hours at 90° C.; then the solvent is eliminated in vacuo usingthe rotary evaporator. The residue is combined with water and extractedthree times with ethyl acetate. The combined organic phases areextracted twice with sat. ammonium chloride solution, then dried oversodium sulphate and filtered. The filtrate is evaporated to dryness i.vac. The residue is purified by reversed phase HPLC.

Yield: 1.95 g (12%) R_(t) value: 4.26 min C₁₂H₁₄N₂O₄ (250.25) Massspectrum: (M+H)⁺=251

(c) 3-(4-amino-2-methyl-phenyl)-[1,3]oxazepan-2-one

1.95 g (7.79 mmol) 3-(2-methyl-4-nitro-phenyl)-[1,3]oxazepan-2-one aredissolved in 200 ml of tetrahydrofuran and combined with 700 mg Raneynickel. The mixture is hydrogenated in a Parr apparatus at ambienttemperature at 1 bar hydrogen pressure for four hours. Then the catalystis filtered off and the filtrate is evaporated down i. vac.

Yield: quantitative R_(t) value: 2.76 min C₁₂H₁₆N₂O₂ (220.27) Massspectrum: (M+H)⁺=221

(d)3-[2-methyl-4-(4-nitro-2-oxo-pyrrolidin-1-yl)-phenyl]-[1,3]oxazepan-2-one

1.52 g (6.89 mmol) 3-(4-amino-2-methyl-phenyl)-[1,3]oxazepan-2-one and1.0 g (6.89 mmol) methyl 3-nitro-but-3-enoate (prepared analogously toM. Mühlstädt, B. Schulze J. Prakt. Chem. 1971, 313(4), 745-753) aremelted together at 130° C. for 50 minutes. The mixture is allowed tocool and dissolved in DMF. The solution is acidified with TFA andpurified by chromatography using reversed phase HPLC.

Yield: 100 mg (4%) R_(t) value: 3.93 min C₁₆H₁₉N₃O₅ (333.34) Massspectrum: (M+H)⁺=334

(e)3-[4-(4-amino-2-oxo-pyrrolidin-1-yl)-2-methyl-phenyl]-[1,3]oxazepan-2-one-trifluoroacetate

36 mg (150 μmol) nickel(II)chloride-hexahydrate are dissolved in 2 ml ofmethanol by treatment with ultrasound and combined with 15 mg (396 μmol)sodium borohydride. 100 mg (300 μmol) of3-[2-methyl-4-(4-nitro-2-oxo-pyrrolidin-1-yl)-phenyl]-[1,3]-oxazepan-2-oneare dissolved in 2 ml of methanol and added in two batches to thereaction solution. After the first quantity has been added a further 21mg (555 μmol) sodium borohydride are put in. Then the remaining solutionof the nitro compound is added in sequence followed by another 21 mg(555 μmol) of sodium borohydride. The mixture is then stirred for fivehours at ambient temperature, acidified with TFA and purified bychromatography through reversed phase HPLC.

Yield: 30 mg (33%) R_(t) value: 3.10 min C₁₆H₂₁N₃O₃ (303.36) Massspectrum: (M+H)⁺=304

(f) 5-bromo-thiophene-2-carboxylicacid-{1-[3-methyl-4-(2-oxo-[1,3]oxazepan-3-yl)-phenyl-5-oxo-pyrrolidin-3-yl}-amide

Prepared from3-[4-(4-amino-2-oxo-pyrrolidin-1-yl)-2-methyl-phenyl]-[1,3]-oxazepan-2-one-trifluoroacetate,TBTU, NMM and 5-bromo-thiophene-2-carboxylic acid analogously to Example1g and subsequent purification by reversed-phase chromatography.

Yield: 63% R_(t) value : 4.50 min C₂₁H₂₂BrN₃O₄S (492.39) Mass spectrum:(M+H)⁺=492/494 (bromine isotope)

EXAMPLE 26 (R)-5-bromo-thiophene-2-carboxylicacid-{1-[6-methyl-5-(3-oxo-morpholin-4-yl)-pyridin-2-yl]-5-oxo-pyrrolidin-3-yl}-amide

(a) benzyl(R)-[1-hydroxymethyl-2-(6-methyl-5-nitro-pyridin-2-yl-carbamoyl)-ethyl]-carbamate

Prepared analogously to Example 2b from6-methyl-5-nitro-pyridin-2-ylamine and benzyl(R)-(5-oxo-tetrahydrofuran-3-yl)-carbamate with trimethylaluminiumactivation in THF and subsequent purification by chromatography onsilica gel (dichloromethane/methanol 20:1).

Yield: 13% R_(f) value: 0.29 (silica gel, dichloromethane/methanol 95:5)R_(t) value: 2.81 min C₁₈H₂₀N₄O₆ (388.38) Mass spectrum: (M+H)⁺=389

(b) benzyl(R)-[1-(6-methyl-5-nitro-pyridin-2-yl)-5-oxo-pyrrolidin-3-yl]-carbamate

Prepared analogously to Example 2c from benzyl(R)-[1-hydroxymethyl-2-(6-methyl-5-nitro-pyridin-2-yl-carbamoyl)-ethyl]-carbamatewith di-tert.-butyl azodicarboxylate and tributylphosphine in THF andsubsequent purification by reversed-phase chromatography.

Yield: 71% R_(t) value: 3.08 min C₁₈H₁₈N₄O₅ (370.36) Mass spectrum:(M+H)⁺=371

(c) benzyl(R)-[1-(5-amino-6-methyl-pyridin-2-yl)-5-oxo-pyrrolidin-3-yl]-carbamate

250 mg (0.68 mmol) benzyl(R)-[1-(6-methyl-5-nitro-pyridin-2-yl)-5-oxo-pyrrolidin-3-yl]-carbamateare dissolved in 4 ml THF and 5 mL methanol and combined with 50 mgRaney nickel. The mixture is hydrogenated in a Parr apparatus at ambienttemperature at 1 bar hydrogen pressure for four hours. Then the catalystis filtered off and the filtrate is evaporated down i. vac..

Yield: 200 mg (87%) R_(f) value: 0.25 (silica gel,dichloromethane/methanol 95:5) C₁₈H₂₀N₄O₃ (340.38) Mass spectrum:(M+H)⁺=341

(d) benzyl(R)-(1{5-[2-(2-chloro-ethoxy)-acetylamino]-6-methyl-pyridin-2-yl}-5-oxo-pyrrolidin-3-yl)-carbamate

200 mg (0.59 mmol) of benzyl(R)-[1-(5-amino-6-methyl-pyridin-2-yl)-5-oxo-pyrrolidin-3-yl]-carbamateand 112 mg (0.71 mmol) of (2-chloro-ethoxy)-acetyl-chloride aredissolved in 2 ml THF, then 246 μl (1.78 mmol) triethylamine is meteredin and the mixture is stirred for one hour at ambient temperature. Thenthe reaction mixture is combined with water and extracted three timeswith ethyl acetate. The combined organic phases are dried over sodiumsulphate, filtered off and the filtrate is evaporated to dryness.

Yield: quantitative R_(t) value: 2.90 min C₂₂H₂₅ClN₄O₅ (460.91) Massspectrum: (M+H)⁺=461/463 (chlorine isotopes)

(e) benzyl(R)-{1-[6-methyl-5-(3-oxo-morpholin-4-yl)-pyridin-2-yl]-5-oxo-pyrrolidin-3-yl}-carbamate

50 mg (0.11 mmol) of benzyl(R)-1-{5-[2-(2-chloro-ethoxy)-acetylamino]-6-methyl-pyridin-2-yl}-5-oxo-pyrrolidin-3-yl)-carbamateare dissolved in 1 ml DMF, then 19.0 mg (0.17 mmol)potassium-tert.-butoxide and 1 mg sodium iodide are added. The reactionmixture is heated to 60° C. and stirred for 3 hours at this temperature.Then it is cooled to ambient temperature, the solution is acidified withTFA and purified by reversed-phase chromatography.

Yield: 40 mg (87%) R_(t) value: 2.65 min C₂₂H₂₄N₄O₅ (424.45) Massspectrum: (M+H)⁺=425

(f)(R)-4-[6-(4-amino-2-oxo-pyrrolidin-1-yl)-2-methyl-pyridin-3-yl]-morpholin-3-one

230 mg (0.54 mmol) of benzyl(R)-{1-[6-methyl-5-(3-oxo-morpholin-4-yl)-pyridin-2-yl]-5-oxo-pyrrolidin-3-yl}-carbamateare dissolved in 5 ml THF and 10 mL methanol and combined with 180 mgpalladium/charcoal. The mixture is hydrogenated in a Parr apparatus atambient temperature at 1 bar hydrogen pressure for 3 hours. Then thecatalyst is filtered off and the filtrate is evaporated down i. vac.

Yield: 148 mg (94%) R_(f) value: 0.04 (silica gel,dichloromethane/methanol 95:5) R_(t) value: 1.34 min C₁₄H₁₈N₄O₃ (290.32)Mass spectrum: (M+H)⁺=291

(g) (R)-5-bromo-thiophene-2-carboxylicacid-{1-[6-methyl-5-(3-oxo-morpholin-4-yl)-pyridin-2-yl]-5-oxo-pyrrolidin-3-yl}-amide

Prepared from(R)-4-[6-(4-amino-2-oxo-pyrrolidin-1-yl)-2-methyl-pyridin-3-yl]-morpholin-3-one,TBTU, NMM and 5-bromo-thiophene-2-carboxylic acid analogously to Example1g and subsequent purification by reversed-phase chromatography.

Yield: 64% R_(t) value: 2.71 min C₁₉H₁₉BrN₄O₄ S (479.35) Mass spectrum:(M+H)⁺+=479/481 (bromine isotope)

The following compounds were prepared analogously:

No. Structural formula Yield Mass peak(s) R_(f) value or R_(t) Name 27

Σ: 5.0% (M − H)⁻ = 462/464 (bromine isotope) 2.58 min(R)-5-bromo-thiophene-2-carboxylic acid-{1 -[4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide 28

Σ: 3.9% (M − H)⁻ = 423 2.61 min (R)-5-ethynyl-thiophene-2-carboxylicacid-{5-oxo-1-[6-methyl-5-(3-oxo-morpholin-4-yl)-pyridin-2-yl]-pyrrolidin-3-yl}-amide 29

Σ: 4.4% (M − H)⁻ = 433/435 (bromine isotope) 2.66 min(R)-5-chloro-thiophene-2-carboxylicacid-{1-[6-methyl-5-(3-oxo-morpholin-4-yl)-pyridin-2-yl]-5-oxo-pyrrolidin-3-yl}-amide 30

Σ: 5.6% (M − H)⁻ = 408 2.56 min (R)-5-ethynyl-thiophene-2-carboxylicacid-{5-oxo-1-[4-(3-oxo-morpholin-4- yl)-phenyl]-pyrrolidin-3-yl}-amide31

Σ: 3.2% (M − H)⁻ = 418/420 (chlorine isotope) 2.56 min(R)-5-chloro-thiophene-2-carboxylic acid-{5-oxo-1-[4-(3-oxo-morpholin-4-yl)-phenyl]-pyrrolidin-3-yl}-amide 32

Σ: 4.6% (M + H)⁺ = 454/456 (bromine isotope) 2.81 min(R)-4-bromo-thiophene-2-carboxylic acid-{1-[5-oxo-4-(3-oxo-morpholin-4-yl)-phenyl]-pyrrolidin-3-yl}-amide 42

Σ: 0.7% (M + H)⁺ = 513/515 (bromine isotope) xxx min(R)-4-bromo-thiophene-2-carboxylic acid-{1-[4-(1,1-dioxo-1□⁶-[1,2,6]thiadiazinan-2-yl)-3-methyl-phenyl]-5-oxo-pyrrolidin-3-yl}-amide43

Σ: 2.1% (M + H)⁺ = 492/494 (bromine isotope) 2.76 min(R)-4-bromo-thiophene-2-carboxylic acid-{1-[3-methyl-4-(3-oxo-[1,4]oxazepan-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide

EXAMPLE 38 (R)-5-chloro-thiophene-2-carboxylicacid-{1-[4-(1,1-dioxo-1□⁶-[1,2]thiazinan-2-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide

(a) 2-(4-nitrophenyl)-[1,2]thiazinane-1,1-dioxide

500 mg (3.7 mmol) [1,2]thiazinane-1,1-dioxide, dissolved in 10 ml DMF,are added to a suspension of 163 mg sodium hydride dispersion in mineraloil (60%, 4.07 mmol) in 5 ml DMF. The mixture is stirred for 15 minutes,then a solution of 522 mg (3.7 mmol) 1-fluoro-4-nitrobenzene in 10 mlDMF is added dropwise. After two hours the reaction mixture is pouredonto ice water. The solid is filtered off, washed with water and dried.

Yield: 707 mg (75%) R_(t) value: 4.45 min C₁₀H₁₂N₂O₄S (256.28) Massspectrum: (M+H)⁺=257

(b) 4-(1,1-dioxo-1□⁶-[1,2]thiazinan-2-yl)-phenylamine

Prepared from 2-(4-nitrophenyl)-[1,2]thiazinan-1,1-dioxide analogouslyto Example 1c with Raney nickel in methanol under 50 psi hydrogenpressure.

Yield: 91% R_(t) value: 2.94 min C₁₀H₁₄BrN₂O₂ S (226.30) Mass spectrum:(M+H)⁺=227

(c) benzyl(R)-(1-{[4-(1,1-dioxo-1□⁶-[1,2]thiazinan-2-yl)-phenylcarbamoyl]-methyl}-2-hydroxy-ethyl)-carbamate

Prepared analogously to Example 2b from4-(1,1-dioxo-1□⁶-[1,2]thiazinan-2-yl)-phenylamine and benzyl(R)-(5-oxo-tetrahydrofuran-3-yl)-carbamate with trimethylaluminiumactivation in THF and subsequent purification by chromatography onsilica gel (dichloromethane/methanol 20:1).

Yield: 22% R_(t) value: 4.08 min (K-factor: 5.087) C₂₂H₂₇N₃O₆S (461.53)Mass spectrum: (M+H)⁺=462

(d) benzyl(R)-{1-[4-(1,1-dioxo-1□⁶-[1,2]thiazininan-2-yl)-phenyl]-5-oxo-pyrrolidin-2-yl}-carbamate

Prepared analogously to Example 2c from benzyl(R)-(1-{[4-(1,1-dioxo-1□⁶-[1,2]thiazinan-2-yl)-phenylcarbamoyl]-methyl}-2-hydroxy-ethyl)-carbamatewith di-tert.-butyl azodicarboxylate and tributylphosphine in THF andsubsequent purification by chromatography on silica gel(dichloromethane/methanol 20:1).

Yield: 84% R_(t) value: 2.88 min C₁₈H₁₈N₄O₅ (443.52) Mass spectrum:(M+H)⁺=444

(e)(R)-4-amino-1-[4-(1,1-dioxo-1□⁶-[1,2]thiazinan-2-yl)-phenyl]-pyrrolidin-2-one

Prepared analogously to Example 2d from benzyl(R)-{1-[4-(1,1-dioxo-1-□⁶-[1,2]thiazininan-2-yl)-phenyl]-5-oxo-pyrrolidin-2-yl}-carbamateand subsequent purification by chromatography on silica gel(dichloromethane/methanol 20:1).

Yield: 43% R_(t) value: 1.85 min C₁₄H₁₉N₃O₃S (309.39) Mass spectrum:(M+H)⁺=310

(f) (R)-5-chloro-thiophene-2-carboxylicacid-{1-[4-(1,1-dioxo-1□⁶-[1,2]thiazinan-2-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide

Prepared from(R)-4-amino-1-[4-(1,1-dioxo-1□⁶-[1,2]thiazinan-2-yl)-phenyl]-pyrrolidin-2-one,TBTU, NMM and 5-chloro-thiophene-2-carboxylic acid analogously toExample 1g and subsequent purification by reversed-phase chromatography.

Yield: 61% R_(t) value: 2.89 min C₁₉H₂₀ClN₃O₄S₂ (453.97) Mass spectrum:(M+H)⁺=454/456 (chlorine isotopes)

The following compounds were prepared analogously:

No. Structural formula Yield Mass peak(s) R_(f) value or R_(t) Name 39

Σ: 2.9% (M − H)⁻= 498/500 (bromine isotope) 2.91 min(R)-5-bromo-thiophene-2-carboxylic acid-{1-[4-(1,1-dioxo-1□⁶-[1,2]thiazinan-2-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide 40

Σ: 2.2% (M − H)⁻=444 2.82 min (R)-5-ethynyl-thiophene-2-carboxylicacid-{1-[4-(1,1-dioxo-1□⁶-[1,2]thiazinan-2-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide

EXAMPLE 49 5-bromo-thiophene-2-carboxylicacid-{(3R,4S)-4-hydroxy-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide

(a) 5-bromo-thiophene-2-carboxylicacid-{(3R,4S)-4-hydroxy-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide

476 μl butyllithium solution (1.6 M in n-hexane) are added dropwise at0° C. to a solution of 105 μl diisopropylamine (747 μmol) in 5 ml THF;the mixture is stirred for 10 minutes at this temperature and thencooled to −80° C. Then 100 mg of (R)-5-bromo-thiophene-2-carboxylicacid-{1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide(209 μmol), dissolved in 1 ml THF, are added dropwise. The mixture isstirred for 30 minutes at −80° C. 77 mg(2R,8aS)-(+)-(camphorylsulphonyl)-oxaziridine (336 μmol), dissolved in 1ml THF, are added dropwise to this mixture. Within 1.5 hours the mixtureis heated to −60° C. 0.5 ml saturated ammonium chloride solution isadded and the mixture is further heated to ambient temperature. Themixture is combined with water and extracted three times with ethylacetate. The combined organic phases are dried over sodium sulphate,filtered off and the filtrate is evaporated to dryness. The residue ispurified by reversed-phase chromatography.

Yield: 31 mg (30%) R_(t) value: 2.53 min C₂₀H₂₀BrN₃O₅S (494.36) Massspectrum: (M+H)⁺=494/496 (bromine isotope)

EXAMPLE 65 5-chloro-thiophene-2-carboxylicacid-{3-methyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide

(a) 5-chloro-thiophene-2-carboxylicacid-(3-methyl-5-oxo-tetrahydro-furan-3-yl)-amide

4.45 g (39 mmol) methallyl acetate are placed under argon in apressurised vessel at −60° C. and combined with 3 ml (34.5 mmol)chlorosulphonyl isocyanate. The pressurised vessel is sealed and themixture is allowed to heat up to +10° C. within 20 hours. It is thencooled to −60° C. again and the jelly-like mixture is carefully rinsedwith 15 ml of ethanol in 25 ml of 5N sodium hydroxide solution. Afterthe initial exothermic reaction has died down the mixture is stirred forone hour at 60° C. Then it is acidified with 20 ml of conc. hydrochloricacid, refluxed for one hour and the solvent is evaporated off underreduced pressure. The viscous residue is dissolved in 60 ml of water andextracted twice with ethyl acetate. The aqueous phase is thenlyophilised. 12.6 g of a colourless solid is obtained which is suspendedin 80 ml DCM.

5.6 g (34.5 mmol) 5-chlorothiophene-2-carboxylic acid are dissolved in20 ml of thionyl chloride, combined with one drop of DMF, and refluxedfor one hour with stirring. Then excess solvent is eliminated using therotary evaporator. The crude product, dissolved in 10 ml DCM, is addeddropwise to the suspension at −78° C. Then 20 ml (0.14 mol)triethylamine is added and the mixture is heated to ambient temperaturefor four hours. The mixture is then kept at reflux temperature for afurther hour.

The reaction mixture is cooled and the solvents are distilled off. Theresidue is dissolved in ethyl acetate and washed with 1N hydrochloricacid. The aqueous phase is extracted three times with ethyl acetate. Thecombined organic phases are washed with 1N sodium hydroxide solution andsaturated saline solution, dried over sodium sulphate and evaporated todryness. The residue thus obtained is purified by chromatography byRP-HPLC. A white solid is obtained.

Yield: 1.48 g (17% over three steps) R_(t) value: 2.70 min R_(f) value:0.70 (silica gel, dichloromethane/methanol 9:1) C₁₀H₁₀ClNO₃S (259.71)Mass spectrum: (M+H)⁺=260/262 (chlorine isotopes)

(b) 5-chloro-thiophene-2-carboxylicacid-(2-hydroxy-1-methyl-1-{[3-methyl-4-(3-oxo-morpholin-4-yl)-phenylcarbamoyl]-methyl}-ethyl)-amide

Prepared analogously to Example 2b from4-(4-amino-2-methyl-phenyl)-morpholin-3-one and5-chloro-thiophene-2-carboxylicacid-(3-methyl-5-oxo-tetrahydro-furan-3-yl)-amide withtrimethylaluminium activation in THF and subsequent purification bychromatography on silica gel (dichloromethane/methanol 20:1).

Yield: 67% R_(f) value: 0.30 (silica gel, dichloromethane/methanol 95:5)C₂₁H₂₄ClN₃O₅S (465.95) Mass spectrum: (M+H)⁺=466/468 (chlorine isotopes)

(c) 5-chloro-thiophene-2-carboxylicacid-{3-methyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide

Prepared analogously to Example 2c from 5-chloro-thiophene-2-carboxylicacid-(2-hydroxy-1-methyl-1-{[3-methyl-4-(3-oxo-morpholin-4-yl)-phenylcarbamoyl]-methyl}-ethyl)-amidewith diisopropyl azodicarboxylate and triphenylphosphine in THF andsubsequent purification by chromatography on silica gel(dichloromethane/methanol 50:1).

Yield: 18% R_(t) value: 2.54 min C₂₁H₂₂ClN₃O₄S (447.94) Mass spectrum:(M+H)⁺=448/450 (chlorine isotopes)

1. A compound of the formula

wherein, A denotes a group of the formula

wherein m is the number 1 or 2, R^(8a) in each case independently of oneanother denote a hydrogen or halogen atom or a C₁₋₅-alkyl, hydroxy,hydroxy-C₁₋₅-alkyl, C₁₋₅-alkoxy, C₁₋₅-alkoxy-C₁₋₅-alkyl, amino,C₁₋₅-alkylamino, di-(C₁₋₅-alkyl)-amino, amino-C₁₋₅-alkyl,C₁₋₅-alkylamino-C₁₋₅-alkyl, di-(C₁₋₅-alkyl)-amino-C₁₋₅-alkyl,aminocarbonyl, C₁₋₅-alkylaminocarbonyl, di-(C₁₋₅-alkyl)-aminocarbonyl orC₁₋₅-alkylcarbonylamino group, while in the previously mentionedsubstituted 5- to 7-membered groups A the heteroatoms F, Cl, Br, I, O orN optionally introduced with R^(8a) as substituents are not separated byprecisely one carbon atom from a heteroatom selected from among N, O andS, R^(8b) each independently of one another denote a hydrogen atom or aC₁₋₅-alkyl group, R^(8c) each independently of one another denote ahydrogen atom, a C₁₋₅-alkyl, C₁₋₅-alkylcarbonyl, C₁₋₅-alkyloxycarbonylor C₁₋₅-alkylsulphonyl group, X¹ denotes a carbonyl, thiocarbonyl,C═NR^(8c), C═N—OR^(8c), C═N—NO₂, C═N—CN or sulphonyl group, X² denotesan oxygen atom or an —NR^(8b) group, X³ denotes a carbonyl,thiocarbonyl, C═NR^(8c), C═N—OR^(8c), C═N—NO₂, C═N—CN or sulphonylgroup, X⁴ denotes an oxygen or sulphur atom or an —NR^(8c) group, X⁵denotes an oxygen atom or a —CH₂, —CHR^(8a) or —NR^(8c) group, R¹denotes a hydrogen or halogen atom, a C₁₋₃-alkyl or C₁₋₃-alkoxy group,while the hydrogen atoms of the C₁₋₃-alkyl or C₁₋₃-alkoxy group mayoptionally be wholly or partly replaced by fluorine atoms, aC₂₋₃-alkenyl, C₂₋₃-alkynyl, nitrile, nitro or amino group, R² denotes ahydrogen or halogen atom or a C₁₋₃-alkyl group, X denotes a nitrogenatom or a CH group, R³ denotes a hydrogen atom or a C₁₋₃-alkyl group, R⁴and R⁵ each independently of one another denote a hydrogen atom, ahydroxy group, a OR⁹ group, a C₂₋₆-alkenyl or C₂₋₆-alkynyl group, astraight-chain or branched C₁₋₆-alkyl group, while the hydrogen atoms ofthe straight-chain or branched C₁₋₆-alkyl group may optionally be whollyor partly replaced by fluorine atoms, and which may optionally besubstituted by a C₃₋₅-cycloalkyl group, a nitrile, hydroxy, aC₁₋₅-alkyloxy group, while the hydrogen atoms of the C₁₋₅-alkyloxy groupmay optionally be wholly or partly replaced by fluorine atoms, anallyloxy, propargyloxy, benzyloxy, C₁₋₅-alkylcarbonyloxy,C₁₋₅-alkyloxycarbonyloxy, carboxy-C₁₋₅-alkyloxy,C₁₋₅-alkyloxycarbonyl-C₁₋₅-alkyloxy, mercapto, C₁₋₅-alkylsulphanyl,C₁₋₅-alkylsulphonyl, carboxy, C₁₋₅-alkyloxycarbonyl, aminocarbonyl,C₁₋₅-alkylaminocarbonyl, di-(C₁₋₅-alkyl)-aminocarbonyl,C₃₋₆-cycloalkyleneiminocarbonyl, aminosulphonyl,C₁₋₅-alkylaminosulphonyl, di-(C₁₋₅-alkyl)-aminosulphonyl,C₃₋₆-cycloalkyleneiminosulphonyl, amino, C₁₋₅-alkylamino,di-(C₁₋₅-alkyl)-amino, C₁₋₅-alkylcarbonylamino,C₁₋₅-alkyl-sulphonylamino, N-(C₁₋₅-alkylsulphonyl)-C₁₋₅-alkylamino orC₃₋₆-cycloalkylcarbonylamino group, while the 6- to 7-membered cyclicgroups of the C₃₋₆-cycloalkyleneiminocarbonyl group in the cyclic moietya methylene group in the 4 position of a 6- or 7-memberedcycloalkyleneimino group may be replaced by an oxygen or sulphur atom,by a carbonyl, sulphinyl, sulphonyl or —NR^(8c) group and additionally amethylene group adjacent to an above-mentioned —NR^(8c) group may bereplaced by a carbonyl group, a phenyl, or heteroaryl group which mayoptionally be mono- to trisubstituted in the phenyl or heteroaryl moietyby identical or different substituents selected from among halogenatoms, C₁₋₅-alkyl, di-(C₁₋₅-alkyl)-amino, hydroxy, C₁₋₅-alkyloxy, mono-,di- or trifluoromethoxy, carboxy- and C₁₋₅-alkyloxycarbonyl groups, aphenyl-C₁₋₅-alkyl or heteroaryl-C₁₋₅-alkyl group, which may optionallybe mono- to trisubstituted in the phenyl or heteroaryl moiety byidentical or different substituents selected from among halogen atoms,C₁₋₅-alkyl, di-(C₁₋₅-alkyl)-amino, hydroxy, C₁₋₅-alkyloxy, mono-, di- ortrifluoromethoxy, carboxy- and C₁₋₅-alkyloxycarbonyl groups, and whichmay optionally be substituted in the C₁₋₅-alkyl-moiety by a hydroxy, aC₁₋₅-alkyloxy group, while the hydrogen atoms of the C₁₋₅-alkyloxy groupmay optionally be wholly or partly replaced by fluorine atoms, anallyloxy, propargyloxy, benzyloxy, C₁₋₅-alkylcarbonyloxy,C₁₋₅-alkyloxycarbonyloxy, carboxy-C₁₋₅-alkyloxy, or aC₁₋₅-alkyloxycarbonyl-C₁₋₅-alkyloxy group; a 3- to 7-memberedcycloalkyl, cycloalkyleneimino, cycloalkyl-C₁₋₅-alkyl orcycloalkyleneimino-C₁₋₃-alkyl group, wherein in 4- to 7-membered cyclicgroups in the cyclic moiety a methylene group may optionally be replacedby an —N(R^(8c)) group, an oxygen or sulphur atom or a —S(O) or —S(O)₂group, or wherein in 4- to 7-membered cyclic groups in the cyclic moietytwo adjacent methylene groups together may optionally be replaced by a—C(O)N(R^(8b)) or —S(O)₂N(R^(8b)) group, or wherein in 6- to 7-memberedcyclic groups in the cyclic moiety three adjacent methylene groupstogether may optionally be replaced by a substituted —OC(O)N(R^(8b)) or—N(R^(8b))C(O)N(R^(8b)) or —N(R ^(8b))S(O)₂N(R^(8b)) group, with theproviso that a 3- to 7-membered cycloalkyl, cycloalkyleneimino,cycloalkyl-C₁₋₅-alkyl or cycloalkyleneimino-C₁₋₃-alkyl group ashereinbefore defined wherein two heteroatoms from the group oxygen andnitrogen are separated from one another by precisely one optionallysubstituted —CH₂ group, is excluded, while a 3- to 7-memberedcycloalkyl, cycloalkyleneimino, cycloalkyl-C₁₋₅-alkyl orcycloalkyleneimino-C₁₋₃-alkyl group as hereinbefore defined may besubstituted at one or two —CH₂ groups by one or two C₁₋₃-alkyl groups ineach case, with the proviso that R⁴ and R⁵ may not simultaneously bedefined as hydroxy or OR⁹ groups, or R⁴ and R⁵ together with the carbonatom to which they are bound form a C₃₋₈-cycloalkyl or C₃₋₈-cycloalkenylgroup, while one of the methylene groups of a C₄₋₈-cycloalkyl group maybe replaced by an oxygen or sulphur atom or an —N(R^(8c)), or acarbonyl, sulphinyl or sulphonyl group, and/or two directly adjacentmethylene groups of a C₄₋₈-cycloalkyl group may together be replaced bya —C(O)N(R^(8b)) or —S(O)₂N(R^(8b)) group, and/or three directlyadjacent methylene groups of a C₆₋₈-cycloalkyl group may together bereplaced by a —OC(O)N(R^(8b)), —N(R^(8b))C(O)N(R^(8b)) or—N(R^(8b))S(O)₂N(R^(8b)) group, while 1 to 3 carbon atoms of aC₃₋₈-cycloalkyl group may optionally be substituted independently of oneanother by in each case one or two identical or different halogen atomsor C₁₋₅-alkyl, nitrile, hydroxy, C₁₋₅-alkyloxy, C₁₋₅-alkylcarbonyloxy,carboxy-C₁₋₅-alkyl, C₁₋₅-alkyloxycarbonyl-C₁₋₅-alkyl,C₁₋₅-alkylsulphanyl, C₁₋₅-alkylsulphonyl, carboxy,C₁₋₅-alkyloxycarbonyl, aminocarbonyl, C₁₋₅-alkylaminocarbonyl,di-(C₁₋₅-alkyl)-aminocarbonyl, C₃₋₆-cycloalkyleneiminocarbonyl,aminosulphonyl, C₁₋₅-alkylaminosulphonyl,di-(C₁₋₅-alkyl)-aminosulphonyl, C₃₋₆-cycloalkyleneiminosulphonyl, amino,C₁₋₅-alkylamino, di-(C₁₋₅-alkyl)-amino, C₁₋₅-alkylcarbonylamino,C₁₋₅-alkylsulphonylamino, N-(C₁₋₅-alkylsulphonyl)-C₁₋₅-alkylamino orC₃₋₆-cycloalkylcarbonylamino groups, while 1 to 2 carbon atoms of aC₃₋₈-cycloalkenyl group may optionally be substituted independently ofone another by in each case a C₁₋₅-alkyl, nitrile, carboxy-C₁₋₅-alkyl,C₁₋₅-alkyloxycarbonyl-C₁₋₅-alkyl, carboxy, C₁₋₅-alkyloxycarbonyl,aminocarbonyl, C₁₋₅-alkylaminocarbonyl, di-(C₁₋₅-alkyl)-aminocarbonyl,C₃₋₆-cycloalkyleneiminocarbonyl, aminosulphonyl,C₁₋₅-alkylaminosulphonyl, di-(C₁₋₅-alkyl)-aminosulphonyl,C₃₋₆-cycloalkyleneiminosulphonyl groups, and 1 to 2 carbon atoms of aC₄₋₈-cycloalkenyl group which are not bound by a double bond to anothercarbon atom, may optionally be substituted independently of one anotherby a fluorine atom or a hydroxy, C₁₋₅-alkyloxy, C₁₋₅-alkylcarbonyloxy,C₁₋₅-alkylsulphanyl, C₁₋₅-alkylsulphonyl, amino, C₁₋₅-alkylamino,di-(C₁₋₅-alkyl)-amino, C₁₋₅-alkylcarbonylamino,C₁₋₅-alkylsulphonylamino, N-(C₁₋₅-alkylsulphonyl)-C₁₋₅-alkylamino orC₃₋₆-cycloalkylcarbonylamino groups, with the proviso that aC₃₋₈-cycloalkyl or C₃₋₈-cycloalkenyl group of this kind formed from R⁴and R⁵ together, wherein two heteroatoms in the cyclic group selectedfrom among oxygen and nitrogen are separated from one another byprecisely one optionally substituted —CH₂ group, and/or wherein one orboth methylene groups of the cyclic group, which are directly attachedto the carbon atom to which the groups R⁴ and R⁵ are bound, are replacedby a heteroatom selected from the group among oxygen, nitrogen andsulphur, and/or wherein a substituent bound to the cyclic group, whichis characterised in that a heteroatom selected from among oxygen,nitrogen, sulphur and halogen atom is bound directly to the cyclicgroup, is separated from another heteroatom selected from among oxygen,nitrogen and sulphur, with the exception of the sulphone group, byprecisely one optionally substituted methylene group, and/or wherein twooxygen atoms are joined together directly, is excluded, R⁹ denotes astraight-chain or branched C₁₋₆-alkyl group, while the hydrogen atoms ofthe straight-chain or branched C₁₋₆-alkyl group may optionally be whollyor partly replaced by fluorine atoms, and which may optionally besubstituted by a C₃₋₅-cycloalkyl group, a hydroxy, a C₁₋₅-alkyloxygroup, while the hydrogen atoms of the C₁₋₅-alkyloxy group mayoptionally be wholly or partly replaced by fluorine atoms, an allyloxy,propargyloxy, benzyloxy, C₁₋₅-alkylcarbonyloxy,C₁₋₅-alkyloxycarbonyloxy, carboxy-C₁₋₅-alkyloxy,C₁₋₅-alkyloxycarbonyl-C₁₋₅-alkyloxy, carboxy, C₁₋₅-alkyloxycarbonyl,aminocarbonyl, C₁₋₅-alkylaminocarbonyl, di-(C₁₋₅-alkyl)-aminocarbonyl,C₃₋₆-cycloalkyleneiminocarbonyl, amino, C₁₋₅-alkylamino,di-(C₁₋₅-alkyl)-amino, C₁₋₅-alkylcarbonylamino,C₁₋₅-alkyl-sulphonylamino, N-(C₁₋₅-alkylsulphonyl)-C₁₋₅-alkylamino orC₃₋₆-cycloalkylcarbonylamino group, while the 6- to 7-membered cyclicgroups of the C₃₋₆-cycloalkyleneiminocarbonyl group in the cyclic moietya methylene group in the 4 position of a 6- or 7-memberedcycloalkyleneimino group may be replaced by an oxygen or sulphur atom,by a carbonyl, sulphinyl, sulphonyl or —NR^(8c) group and additionally amethylene group adjacent to an above-mentioned —NR^(8c) group may bereplaced by a carbonyl group, with the proviso that the replacement ofhydrogen atoms of the first carbon atom of the straight-chain orbranched C₁₋₆-alkyl group by substituents from the group comprisingoxygen, sulphur or nitrogen is excluded, a phenyl, heteroaryl,phenyl-C₁₋₅-alkyl or heteroaryl-C₁₋₅-alkyl group, which may optionallybe mono- to trisubstituted in the phenyl or heteroaryl moiety byidentical or different substituents selected from among halogen atoms,C₁₋₅-alkyl, di-(C₁₋₅-alkyl)-amino, hydroxy, C₁₋₅-alkyloxy, mono-, di- ortrifluoromethoxy, carboxy- and C₁₋₅-alkyloxycarbonyl groups, a 3- to7-membered cycloalkyl, cycloalkyl-C₁₋₅-alkyl orcycloalkyleneimino-C₂₋₃-alkyl group, wherein in 4- to 7-membered cyclicgroups in the cyclic moiety a methylene group may optionally be replacedby an —N(R^(8c)) group, an oxygen or sulphur atom or a —S(O) or —S(O)₂group, or wherein in 4- to 7-membered cyclic groups in the cyclic moietytwo adjacent methylene groups together may optionally be replaced by a—C(O)N(R^(8b)) or —S(O)₂N(R^(8b)) group, or wherein in 6- to 7-memberedcyclic groups in the cyclic moiety three adjacent methylene groupstogether may optionally be replaced by a substituted —OC(O)N(R^(8b)) or—N(R^(8b))C(O)N(R^(8b)) or —N(R^(8b))S(O)₂N(R^(8b)) group, with theproviso that a 3- to 7-membered cycloalkyl, cycloalkyl-C₁₋₅-alkyl orcycloalkyleneimino-C₂₋₃-alkyl group as hereinbefore defined wherein twoheteroatoms from the group comprising oxygen and nitrogen are separatedfrom one another by precisely one optionally substituted —CH₂ group, isexcluded, while a 3- to 7-membered cycloalkyl, cycloalkyl-C₁₋₅-alkyl orcycloalkyleneimino-C₂₋₃-alkyl group as hereinbefore defined may besubstituted at one or two —CH₂ groups by one or two C₁₋₃-alkyl groups ineach case, B denotes a group of the formula

Y denotes a nitrogen atom or a CH group, R⁶ denotes a hydrogen, ahalogen atom, a nitrile group, a C₂₋₃-alkenyl, C₂₋₃-alkynyl, aC₁₋₃-alkyl group, or a C₁₋₃-alkoxy group, while the hydrogen atoms ofthe C₁₋₃-alkyl or C₁₋₃-alkoxy group may optionally be wholly or partlyreplaced by fluorine atoms, while, unless otherwise stated, by the term“heteroaryl group” mentioned hereinbefore in the definitions is meant amonocyclic 5- or 6-membered heteroaryl group, while the 6-memberedheteroaryl group contains one, two or three nitrogen atoms and the5-membered heteroaryl group contains an imino group optionallysubstituted by a C₁₋₃-alkyl, phenyl or phenyl-C₁₋₃-alkyl group, or anoxygen or sulphur atom or an imino group optionally substituted by aC₁₋₃-alkyl, phenyl, amino-C₂₋₃-alkyl, C₁₋₃-alkylamino-C₂₋₃-alkyl,di-(C₁₋₃-alkyl)-amino-C₂₋₃-alkyl, a C₃₋₆-cycloalkyleneimino-C₁₋₃-alkylor phenyl-C₁₋₃-alkyl group, or an oxygen or sulphur atom andadditionally a nitrogen atom or an imino group optionally substituted bya C₁₋₃-alkyl or phenyl-C₁₋₃-alkyl group and two or three nitrogen atoms,and moreover a phenyl ring optionally substituted by a fluorine,chlorine or bromine atom, a C₁₋₃-alkyl, hydroxy, C₁₋₃-alkyloxy group,amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino or C₃₋₆-cycloalkyleneiminogroup may be fused to the above-mentioned monocyclic heteroaryl groupsvia two adjacent carbon atoms and the bond is effected via a nitrogenatom or a carbon atom of the heterocyclic moiety or a fused-on phenylring, while, unless otherwise stated, by the term “halogen atom”mentioned hereinbefore in the definitions is meant an atom selected fromamong fluorine, chlorine, bromine and iodine, while the alkyl, alkenyl,alkynyl and alkoxy groups contained in the above-mentioned definitionswhich have more than two carbon atoms, unless otherwise stated, bestraight-chain or branched and the alkyl groups in the previouslymentioned dialkylated groups, for example the dialkylamino groups, maybe identical or different, and the hydrogen atoms of the methyl or ethylgroups contained in the foregoing definitions, unless otherwise stated,may be wholly or partly replaced by fluorine atoms, or a tautomer orsalt thereof.
 2. A compound of the formula I according to claim 1,wherein A denotes a group of the formula

wherein m is the number 1 or 2, R^(8a) each independently of one anotherdenote a hydrogen or halogen atom or a C₁₋₅-alkyl, hydroxy,hydroxy-C₁₋₅-alkyl, C₁₋₅-alkoxy, C₁₋₅-alkoxy-C₁₋₅-alkyl, amino,C₁₋₅-alkylamino, di-(C₁₋₅-alkyl)-amino, amino-C₁₋₅-alkyl,C₁₋₅-alkylamino-C₁₋₅-alkyl, di-(C₁₋₅-alkyl)-amino-C₁₋₅-alkyl,aminocarbonyl, C₁₋₅-alkylaminocarbonyl, di-(C₋₅-alkyl)-aminocarbonyl orC₁₋₅-alkylcarbonylamino group denotes, while in the previously mentionedsubstituted 5- to 7-membered groups A the heteroatoms F, Cl, Br, I, O orN optionally introduced with R^(8a) as substituents are not separated byprecisely one carbon atom from a heteroatom selected from among N, O andS, R^(8b) each independently of one another denote a hydrogen atom or aC₁₋₅-alkyl group, R^(8c) each independently of one another denote ahydrogen atom, a C₁₋₅-alkyl, C₁₋₅-alkylcarbonyl, C₁₋₅-alkyloxycarbonylor C₁₋₅-alkylsulphonyl group, X¹ denotes a carbonyl, thiocarbonyl,C═NR^(8c), C═N—OR^(8c), C═N—NO₂, C═N—CN or sulphonyl group, X² denotesan oxygen atom or an —NR^(8b) group, X³ denotes a carbonyl,thiocarbonyl, C═NR^(8c), C═N—OR^(8c), C═N—NO₂, C═N—CN or sulphonylgroup, X⁴ denotes an oxygen or sulphur atom or an —NR^(8c) group, X⁵denotes an oxygen atom or a —CH₂, —CHR^(8a) or —NR^(8c) group, R¹denotes a hydrogen or halogen atom, a C₁₋₃-alkyl or C₁₋₃-alkoxy group,while the hydrogen atoms of the C₁₋₃-alkyl or C₁₋₃-alkoxy group mayoptionally be wholly or partly replaced by fluorine atoms, aC₂₋₃-alkenyl, C₂₋₃-alkynyl, nitrile, nitro or amino group, R² denotes ahydrogen or halogen atom or a C₁₋₃-alkyl group, X denotes a nitrogenatom or a CH group, R³ denotes a hydrogen atom or a C₁₋₃-alkyl group, R⁴and R⁵ each independently of one another denote a hydrogen atom, ahydroxy group, a OR⁹ group, a C₂₋₆-alkenyl or C₂₋₆-alkynyl group, astraight-chain or branched C₁₋₆-alkyl group, while the hydrogen atoms ofthe straight-chain or branched C₁₋₆-alkyl group may optionally be whollyor partly replaced by fluorine atoms, and which may optionally besubstituted by a C₃₋₅-cycloalkyl group, a nitrile, hydroxy, aC₁₋₅-alkyloxy group, while the hydrogen atoms of the C₁₋₅-alkyloxy groupmay optionally be wholly or partly replaced by fluorine atoms, anallyloxy, propargyloxy, benzyloxy, C₁₋₅-alkylcarbonyloxy,C₁₋₅-alkyloxycarbonyloxy, carboxy-C₁₋₅-alkyloxy,C₁₋₅-alkyloxycarbonyl-C₁₋₅-alkyloxy, mercapto, C₁₋₅-alkylsulphanyl,C₁₋₅-alkylsulphonyl, carboxy, C₁₋₅-alkyloxycarbonyl, aminocarbonyl,C₁₋₅-alkylaminocarbonyl, di-(C₁₋₅-alkyl)-aminocarbonyl,C₃₋₆-cycloalkyleneiminocarbonyl, aminosulphonyl,C₁₋₅-alkylaminosulphonyl, di-(C₁₋₅-alkyl)-aminosulphonyl,C₃₋₆-cycloalkyleneiminosulphonyl, amino, C₁₋₅-alkylamino,di-(C₁₋₅-alkyl)-amino, C₁₋₅-alkylcarbonylamino,C₁₋₅alkyl-sulphonylamino, N-(C₁₋₅-alkylsulphonyl)-C₁₋₅-alkylamino orC₃₋₆-cycloalkylcarbonylamino group, while the 6- to 7-membered cyclicgroups of the C₃₋₆-cycloalkyleneiminocarbonyl group in the cyclic moietya methylene group in the 4 position of a 6- or 7-memberedcycloalkyleneimino group may be replaced by an oxygen or sulphur atom,by a carbonyl, sulphinyl, sulphonyl or —NR^(8c) group and additionally amethylene group adjacent to an above-mentioned —NR^(8c) group may bereplaced by a carbonyl group, a phenyl or heteroaryl group which mayoptionally be mono- to trisubstituted in the phenyl or heteroaryl moietyby identical or different substituents selected from among halogenatoms, C₁₋₅-alkyl, di-(C₁₋₅-alkyl)-amino, hydroxy, C₁₋₅-alkyloxy, mono-,di- or trifluoromethoxy, carboxy- and C₁₋₅-alkyloxycarbonyl groups, aphenyl-C₁₋₅-alkyl or heteroaryl-C₁₋₅-alkyl group, which may optionallybe mono- to trisubstituted in the phenyl or heteroaryl moiety byidentical or different substituents selected from among halogen atoms,C₁₋₅-alkyl, di-(C₁₋₅-alkyl)-amino, hydroxy, C₁₋₅-alkyloxy, mono-, di- ortrifluoromethoxy, carboxy- and C₁₋₅-alkyloxycarbonyl groups, and whichmay optionally be substituted in the C₁₋₅-alkyl-moiety by a hydroxy, aC₁₋₅-alkyloxy group, while the hydrogen atoms of the C₁₋₅-alkyloxy groupmay optionally be wholly or partly replaced by fluorine atoms, anallyloxy, propargyloxy, benzyloxy, C₁₋₅-alkylcarbonyloxy,C₁₋₅-alkyloxycarbonyloxy, carboxy-C₁₋₅-alkyloxy, or aC₁₋₅-alkyloxycarbonyl-C₁₋₅-alkyloxy group; a 3- to 7-memberedcycloalkyl, cycloalkyleneimino, cycloalkyl-C₁₋₅-alkyl orcycloalkyleneimino-C₁₋₃-alkyl group, wherein in 4- to 7-membered cyclicgroups in the cyclic moiety a methylene group may optionally be replacedby an —N(R^(8c)) group, an oxygen or sulphur atom or a —S(O) or —S(O)₂group, or wherein in 4- to 7-membered cyclic groups in the cyclic moietytwo adjacent methylene groups together may optionally be replaced by a—C(O)N(R^(8b)) or —S(O)₂N(R^(8b)) group, or wherein in 6- to 7-memberedcyclic groups in the cyclic moiety three adjacent methylene groupstogether may optionally be replaced by a substituted —OC(O)N(R^(8b)) or—N(R^(8b))C(O)N(R^(8b)) or —N(R^(8b))S(O)₂N(R^(8b)) group, with theproviso that a 3- to 7-membered cycloalkyl, cycloalkyleneimino,cycloalkyl-C₁₋₅-alkyl or cycloalkyleneimino-C₁₋₃-alkyl group ashereinbefore defined wherein two heteroatoms from the group comprisingoxygen and nitrogen are separated from one another by precisely oneoptionally substituted —CH₂ group, is excluded, while a 3- to 7-memberedcycloalkyl, cycloalkyleneimino, cycloalkyl-C₁₋₅-alkyl orcycloalkyleneimino-C₁₋₃-alkyl group as hereinbefore defined may besubstituted at one or two —CH₂ groups by one or two C₁₋₃-alkyl groups ineach case, with the proviso that R⁴ and R⁵ cannot simultaneously bedefined as hydroxy or OR⁹ groups, or R⁴ and R⁵ together with the carbonatom to which they are bound form a C₃₋₈-cycloalkyl or C₃₋₈-cycloalkenylgroup, while one of the methylene groups of a C₄₋₈-cycloalkyl group maybe replaced by an oxygen or sulphur atom or an —N(R^(8c)), or acarbonyl, sulphinyl or sulphonyl group, and/or two directly adjacentmethylene groups of a C₄₋₈-cycloalkyl group may together be replaced bya —C(O)N(R^(8b)) or —S(O)₂N(R^(8b)) group, and/or three directlyadjacent methylene groups of a C₆₋₈-cycloalkyl group may together bereplaced by a —OC(O)N(R^(8b)), —N(R^(8b))C(O)N(R^(8b)) or—N(R^(8b))S(O)₂N(R^(8b)) group, while 1 to 3 carbon atoms of aC₃₋₈-cycloalkyl group may optionally be substituted independently of oneanother by in each case one or two identical or different halogen atomsor C₁₋₅-alkyl, nitrile, hydroxy, C₁₋₅-alkyloxy, C₁₋₅-alkylcarbonyloxy,carboxy-C₁₋₅-alkyl, C₁₋₅-alkyloxycarbonyl-C₁₋₅-alkyl,C₁₋₅-alkylsulphanyl, C₁₋₅-alkylsulphonyl, carboxy,C₁₋₅-alkyloxycarbonyl, aminocarbonyl, C₁₋₅-alkylaminocarbonyl,di-(C₁₋₅-alkyl)-aminocarbonyl, C₃₋₆-cycloalkyleneiminocarbonyl,aminosulphonyl, C₁₋₅-alkylaminosulphonyl,di-(C₁₋₅-alkyl)-aminosulphonyl, C₃₋₆-cycloalkyleneiminosulphonyl, amino,C₁₋₅-alkylamino, di-(C₁₋₅-alkyl)-amino, C₁₋₅-alkylcarbonylamino,C₁₋₅-alkyl-sulphonylamino, N-(C₁₋₅-alkylsulphonyl)-C₁₋₅-alkylamino orC₃₋₆-cycloalkylcarbonylamino groups, while 1 to 2 carbon atoms of aC₃₋₈-cycloalkenyl group may optionally be substituted independently ofone another by in each case a C₁₋₅-alkyl, nitrile, carboxy-C₁₋₅-alkyl,C₁₋₅-alkyloxycarbonyl-C₁₋₅-alkyl, carboxy, C₁₋₅-alkyloxycarbonyl,aminocarbonyl, C₁₋₅-alkylaminocarbonyl, di-(C₁₋₅-alkyl)-aminocarbonyl,C₃₋₆-cycloalkyleneiminocarbonyl, aminosulphonyl,C₁₋₅-alkylaminosulphonyl, di-(C₁₋₅-alkyl)-aminosulphonyl,C₃₋₆-cycloalkyleneiminosulphonyl groups, and 1 to 2 carbon atoms of aC₄₋₈-cycloalkenyl group which are not bound by a double bond to anothercarbon atom may optionally be substituted independently of one anotherby a fluorine atom or a hydroxy, C₁₋₅-alkyloxy, C₁₋₅-alkylcarbonyloxy,C₁₋₅-alkylsulphanyl, C₁₋₅-alkylsulphonyl, amino, C₁₋₅-alkylamino,di-(C₁₋₅-alkyl)-amino, C₁₋₅-alkylcarbonylamino,C₁₋₅-alkylsulphonylamino, N-(C₁₋₅-alkylsulphonyl)-C₁₋₅-alkylamino orC₃₋₆-cycloalkylcarbonyl-amino groups, with the proviso that aC₃₋₈-cycloalkyl or C₃₋₈-cycloalkenyl group of this kind formed from R⁴and R⁵ together, wherein two heteroatoms in the cyclic group selectedfrom among oxygen and nitrogen are separated from one another byprecisely one optionally substituted —CH₂ group, and/or wherein one orboth methylene groups of the cyclic group, which are directly attachedto the carbon atom to which the groups R⁴ and R⁵ are bound, are replacedby a heteroatom from the group comprising oxygen, nitrogen and sulphur,and/or wherein a substituent bound to the cyclic group, which ischaracterised in that a heteroatom selected from among oxygen, nitrogen,sulphur and halogen atom is bound directly to the cyclic group, isseparated from another heteroatom selected from among oxygen, nitrogenand sulphur, with the exception of the sulphone group, by precisely one,optionally substituted methylene group, and/or wherein two oxygen atomsare joined together directly, is excluded, R⁹ denotes a straight-chainor branched C₁₋₆-alkyl group, while the hydrogen atoms of thestraight-chain or branched C₁₋₆-alkyl group may optionally be wholly orpartly replaced by fluorine atoms, and which may optionally besubstituted by a C₃₋₅-cycloalkyl group, a hydroxy, a C₁₋₅-alkyloxygroup, while the hydrogen atoms of the C₁₋₅-alkyloxy group mayoptionally be wholly or partly replaced by fluorine atoms, an allyloxy,propargyloxy, benzyloxy, C₁₋₅-alkylcarbonyloxy,C₁₋₅-alkyloxycarbonyloxy, carboxy-C₁₋₅-alkyloxy,C₁₋₅-alkyloxycarbonyl-C₁₋₅-alkyloxy, carboxy, C₁₋₅-alkyloxycarbonyl,aminocarbonyl, C₁₋₅-alkylaminocarbonyl, di-(C₁₋₅-alkyl)-aminocarbonyl,C₃₋₆-cycloalkyleneiminocarbonyl, amino, C₁₋₅-alkylamino,di-(C₁₋₅-alkyl)-amino, C₁₋₅-alkylcarbonylamino,C₁₋₅-alkyl-sulphonylamino, N-(C₁₋₅-alkylsulphonyl)-C₁₋₅-alkylamino orC₃₋₆-cycloalkylcarbonylamino group, while the 6- to 7-membered cyclicgroups of the C₃₋₆-cycloalkyleneiminocarbonyl group in the cyclic moietya methylene group in the 4 position of a 6- or 7-memberedcycloalkyleneimino group may be replaced by an oxygen or sulphur atom,by a carbonyl, sulphinyl, sulphonyl or —NR^(8c) group and additionally amethylene group adjacent to an above-mentioned —NR^(8c) group may bereplaced by a carbonyl group, with the proviso that the replacement ofhydrogen atoms of the first carbon atom of the straight-chain orbranched C₁₋₆-alkyl group by substituents from the group comprisingoxygen, sulphur or nitrogen is excluded, a phenyl, heteroaryl,phenyl-C₁₋₅-alkyl or heteroaryl-C₁₋₅-alkyl group, which may optionallybe mono- to trisubstituted in the phenyl or heteroaryl moiety byidentical or different substituents selected from among halogen atoms,C₁₋₅-alkyl, di-(C₁₋₅-alkyl)-amino, hydroxy, C₁₋₅-alkyloxy, mono-, di- ortrifluoromethoxy, carboxy- and C₁₋₅-alkyloxycarbonyl groups, a 3- to7-membered cycloalkyl, cycloalkyl-C₁₋₅-alkyl orcycloalkyleneimino-C₂₋₃-alkyl group, wherein in 4- to 7-membered cyclicgroups in the cyclic moiety a methylene group may optionally be replacedby an —N(R^(8c)) group, an oxygen or sulphur atom or a —S(O) or —S(O)₂group, or wherein in 4- to 7-membered cyclic groups in the cyclic moietytwo adjacent methylene groups together may optionally be replaced by a—C(O)N(R^(8b)) or —S(O)₂N(R^(8b)) group, or wherein in 6- to 7-memberedcyclic groups in the cyclic moiety three adjacent methylene groupstogether may optionally be replaced by a substituted —OC(O)N(R^(8b)) or—N(R^(8b))C(O)N(R^(8b)) or —N(R^(8b))S(O)₂N(R^(8b)) group, with theproviso that a 3- to 7-membered cycloalkyl, cycloalkyl-C₁₋₅-alkyl orcycloalkyleneimino-C₂₋₃-alkyl group as hereinbefore defined wherein twoheteroatoms from the group comprising oxygen and nitrogen are separatedfrom one another by precisely one optionally substituted —CH₂ group, isexcluded, while a 3- to 7-membered cycloalkyl, cycloalkyl-C₁₋₅-alkyl orcycloalkyleneimino-C₂₋₃-alkyl group as hereinbefore defined may besubstituted at one or two —CH₂ groups by one or two C₁₋₃-alkyl groups ineach case, B denotes a group of the formula

Y denotes a nitrogen atom or a CH group, R⁶ denotes a hydrogen, ahalogen atom, a nitrile group, a C₂₋₃-alkenyl, C₂₋₃-alkynyl, aC₁₋₃-alkyl group, or a C₁₋₃-alkoxy group, while the hydrogen atoms ofthe C₁₋₃-alkyl or C₁₋₃-alkoxy group may optionally be wholly or partlyreplaced by fluorine atoms, while, unless otherwise stated, by the term“heteroaryl group” mentioned hereinbefore in the definitions is meant amonocyclic 5- or 6-membered heteroaryl group, while the 6-memberedheteroaryl group contains one, two or three nitrogen atoms and the5-membered heteroaryl group contains an imino group optionallysubstituted by a C₁₋₃-alkyl, phenyl or phenyl-C₁₋₃-alkyl group, or anoxygen or sulphur atom or an imino group optionally substituted by aC₁₋₃-alkyl, phenyl, amino-C₂₋₃-alkyl, C₁₋₃-alkylamino-C₂₋₃-alkyl,di-(C₁₋₃-alkyl)-amino-C₂₋₃-alkyl, a C₃₋₆-cycloalkyleneimino-C₁₋₃-alkylor phenyl-C₁₋₃-alkyl group, or an oxygen or sulphur atom andadditionally a nitrogen atom or an imino group optionally substituted bya C₁₋₃-alkyl or phenyl-C₁₋₃-alkyl group and two or three nitrogen atoms,and moreover a phenyl ring optionally substituted by a fluorine,chlorine or bromine atom, a C₁₋₃-alkyl, hydroxy, C₁₋₃-alkyloxy group,amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino or C₃₋₆-cycloalkyleneiminogroup may be fused to the above-mentioned monocyclic heteroaryl groupsvia two adjacent carbon atoms and the bond is effected via a nitrogenatom or a carbon atom of the heterocyclic moiety or a fused-on phenylring, while, unless otherwise stated, by the term “halogen atom”mentioned hereinbefore in the definitions is meant an atom selected fromamong fluorine, chlorine, bromine and iodine, while the alkyl, alkenyl,alkynyl and alkoxy groups contained in the above-mentioned definitionswhich have more than two carbon atoms, unless otherwise stated, may bestraight-chain or branched and the alkyl groups in the previouslymentioned dialkylated groups, for example the dialkylamino groups, maybe identical or different, and the hydrogen atoms of the methyl or ethylgroups contained in the foregoing definitions, unless otherwise stated,may be wholly or partly replaced by fluorine atoms, or a tautomer orsalt thereof.
 3. A compound of the formula I according to claim 1,wherein, A denotes a group of the formula

wherein m is the number 1 or 2, R^(8a) each independently of one anotherdenote a hydrogen or fluorine atom or a C₁₋₃-alkyl, hydroxy,hydroxy-C₁₋₃-alkyl, C₁₋₃-alkoxy, C₁₋₃-alkoxy-C₁₋₃-alkyl, amino,C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino, amino-C₁₋₃-alkyl,C₁₋₃-alkylamino-C₁₋₃-alkyl, or di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl group,while in the previously mentioned substituted 5- to 7-membered groups Athe heteroatoms F, O or N optionally introduced with R^(8a) assubstituents are not separated by precisely one carbon atom from aheteroatom selected from among N, O and S, R^(8b) each independently ofone another denote a hydrogen atom or a C₁₋₃-alkyl group, R^(8c) eachindependently of one another denote a hydrogen atom, a C₁₋₃-alkyl,C₁₋₃-alkylcarbonyl, C₁₋₃-alkyloxycarbonyl or C₁₋₃-alkylsulphonyl group,X¹ denotes a carbonyl, thiocarbonyl, C═NR^(8c), C═N—OR^(8c), C═N—NO₂,C═N—CN or sulphonyl group, X² denotes an oxygen atom or an —NR^(8b)group, X³ denotes a carbonyl, thiocarbonyl, C═NR^(8c), C═N—OR^(8c),C═N—NO₂, C═N—CN or sulphonyl group, X⁴ denotes an oxygen or sulphur atomor an —NR^(8c) group, X⁵ denotes an oxygen atom or a —CH₂, —CHR^(8a) or—NR^(8c) group, R¹ denotes a hydrogen or halogen atom, a C₁₋₃-alkyl orC₁₋₃-alkoxy group, while the hydrogen atoms of the C₁₋₃-alkyl orC₁₋₃-alkoxy group may optionally be wholly or partly replaced byfluorine atoms, a C₂₋₃-alkenyl, C₂₋₃-alkynyl, nitrile, nitro or aminogroup, R² denotes a hydrogen or halogen atom or a methyl group, Xdenotes a nitrogen atom or a CH group, R³ denotes a hydrogen atom or aC₁₋₃-alkyl group, R⁴ and R⁵ each independently of one another denote ahydrogen atom, a hydroxy group, a OR⁹ group, a C₂₋₆-alkenyl orC₂₋₆-alkynyl group, a straight-chain or branched C₁₋₆-alkyl group, whilethe hydrogen atoms of the straight-chain or branched C₁₋₆-alkyl groupmay optionally be wholly or partly replaced by fluorine atoms, and whichmay optionally be substituted by a C₃₋₅-cycloalkyl group, a nitrile,hydroxy, a C₁₋₅-alkyloxy group, while the hydrogen atoms of theC₁₋₅-alkyloxy group may optionally be wholly or partly replaced byfluorine atoms, an allyloxy, propargyloxy, benzyloxy,C₁₋₅-alkylcarbonyloxy, C₁₋₅-alkyloxycarbonyloxy, carboxy-C₁₋₅-alkyloxy,C₁₋₅-alkyloxycarbonyl-C₁₋₅-alkyloxy, mercapto, C₁₋₅-alkylsulphanyl,C₁₋₅-alkylsulphonyl, carboxy, C₁₋₅-alkyloxycarbonyl, aminocarbonyl,C₁₋₅-alkylaminocarbonyl, di-(C₁₋₅-alkyl)-aminocarbonyl,C₃₋₆-cycloalkyleneiminocarbonyl, aminosulphonyl,C₁₋₅-alkylaminosulphonyl, di-(C₁₋₅-alkyl)-aminosulphonyl,C₃₋₆-cycloalkyleneiminosulphonyl, amino, C₁₋₅-alkylamino,di-(C₁₋₅-alkyl)-amino,C₁₋₅-alkylcarbonylamino,C₁₋₅-alkyl-sulphonylamino,N-(C₁₋₅-alkylsulphonyl)-C₁₋₅-alkylamino or C₃₋₆-cycloalkylcarbonylaminogroup, while the 6- to 7-membered cyclic groups of theC₃₋₆-cycloalkyleneiminocarbonyl group in the cyclic moiety a methylenegroup in the 4 position of a 6- or 7-membered cycloalkyleneimino groupmay be replaced by an oxygen or sulphur atom, by a carbonyl, sulphinyl,sulphonyl or —NR^(8c) group and additionally a methylene group adjacentto an above-mentioned —NR^(8c) group may be replaced by a carbonylgroup, a phenyl, heteroaryl, phenyl-C₁₋₅-alkyl or heteroaryl-C₁₋₅-alkylgroup, which may optionally be mono- to trisubstituted in the phenyl orheteroaryl moiety by identical or different substituents selected fromamong halogen atoms, C₁₋₅-alkyl, di-(C₁₋₅-alkyl)-amino, hydroxy,C₁₋₅-alkyloxy, mono-, di- or trifluoromethoxy, carboxy- andC₁₋₅-alkyloxycarbonyl groups, a 3- to 7-membered cycloalkyl,cycloalkyleneimino, cycloalkyl-C₁₋₅-alkyl orcycloalkyleneimino-C₁₋₃-alkyl group, wherein in 4- to 7-membered cyclicgroups in the cyclic moiety a methylene group may optionally be replacedby an —N(R^(8c)) group, an oxygen or sulphur atom or a —S(O) or —S(O)₂group, or wherein in 4- to 7-membered cyclic groups in the cyclic moietytwo adjacent methylene groups together may optionally be replaced by a—C(O)N(R^(8b)) or —S(O)₂N(R^(8b)) group, or wherein in 6- to 7-memberedcyclic groups in the cyclic moiety three adjacent methylene groupstogether may optionally be replaced by a substituted —OC(O)N(R^(8b)) or—N(R^(8b))C(O)N(R^(8b)) or —N(R^(8b))S(O)₂N(R^(8b)) group, with theproviso that a 3- to 7-membered cycloalkyl, cycloalkyleneimino,cycloalkyl-C₁₋₅-alkyl or cycloalkyleneimino-C₁₋₃-alkyl group ashereinbefore defined wherein two heteroatoms from the group comprisingoxygen and nitrogen are separated from one another by precisely oneoptionally substituted —CH₂ group, is excluded, while a 3- to 7-memberedcycloalkyl, cycloalkyleneimino, cycloalkyl-C₁₋₅-alkyl orcycloalkyleneimino-C₁₋₃-alkyl group as hereinbefore defined may besubstituted at one or two —CH₂ groups by one or two C₁₋₃-alkyl groups ineach case, with the proviso that R⁴ and R⁵ cannot simultaneously bedefined as hydroxy or OR⁹ groups, R⁹ denotes a straight-chain orbranched C₁₋₆-alkyl group, while the hydrogen atoms of thestraight-chain or branched C₁₋₆-alkyl group may optionally be wholly orpartly replaced by fluorine atoms, and which may optionally besubstituted by a C₃₋₅-cycloalkyl group, a hydroxy, a C₁₋₅-alkyloxygroup, while the hydrogen atoms of the C₁₋₅-alkyloxy group mayoptionally be wholly or partly replaced by fluorine atoms, an allyloxy,propargyloxy, benzyloxy, C₁₋₅-alkylcarbonyloxy,C₁₋₅-alkyloxycarbonyloxy, carboxy-C₁₋₅-alkyloxy,C₁₋₅-alkyloxycarbonyl-C₁₋₅-alkyloxy, carboxy, C₁₋₅-alkyloxycarbonyl,aminocarbonyl, C₁₋₅-alkylaminocarbonyl, di-(C₁₋₅-alkyl)-aminocarbonyl,C₃₋₆-cycloalkyleneiminocarbonyl, amino, C₁₋₅-alkylamino,di-(C₁₋₅-alkyl)-amino, C₁₋₅-alkylcarbonylamino,C₁₋₅-alkylsulphonylamino, N-(C₁₋₅-alkylsulphonyl)-C₁₋₅-alkylamino orC₃₋₆-cycloalkylcarbonylamino group, while the 6- to 7-membered cyclicgroups of the C₃₋₆-cycloalkyleneiminocarbonyl group in the cyclic moietya methylene group in the 4 position of a 6- or 7-memberedcycloalkyleneimino group by an oxygen or sulphur atom may be replaced bya carbonyl, sulphinyl, sulphonyl or —NR^(8c) group and additionally amethylene group adjacent to an above-mentioned —NR^(8c) group may bereplaced by a carbonyl group, with the proviso that the replacement ofhydrogen atoms of the first carbon atom of the straight-chain orbranched C₁₋₆-alkyl group by substituents from the group comprisingoxygen, sulphur or nitrogen is excluded, a phenyl or heteroaryl groupwhich may optionally be mono- to trisubstituted in the phenyl orheteroaryl moiety by identical or different substituents selected fromamong halogen atoms, C₁₋₅-alkyl, di-(C₁₋₅-alkyl)-amino, hydroxy,C₁₋₅-alkyloxy, mono-, di- or trifluoromethoxy, carboxy- andC₁₋₅-alkyloxycarbonyl groups, a phenyl-C₁₋₅-alkyl orheteroaryl-C₁₋₅-alkyl group, which may optionally be mono- totrisubstituted in the phenyl or heteroaryl moiety by identical ordifferent substituents selected from among halogen atoms, C₁₋₅-alkyl,di-(C₁₋₅-alkyl)-amino, hydroxy, C₁₋₅-alkyloxy, mono-, di- ortrifluoromethoxy, carboxy- and C₁₋₅-alkyloxycarbonyl groups, and whichmay optionally be substituted in the C₁₋₅-alkyl-moiety by a hydroxy, aC₁₋₅-alkyloxy group, while the hydrogen atoms of the C₁₋₅-alkyloxy groupmay optionally be wholly or partly replaced by fluorine atoms, anallyloxy, propargyloxy, benzyloxy, C₁₋₅-alkylcarbonyloxy,C₁₋₅-alkyloxycarbonyloxy, carboxy-C₁₋₅-alkyloxy, or aC₁₋₅-alkyloxycarbonyl-C₁₋₅-alkyloxy group; a 3- to 7-memberedcycloalkyl, cycloalkyl-C₁₋₅-alkyl or cycloalkyleneimino-C₂₋₃-alkylgroup, wherein in 4- to 7-membered cyclic groups in the cyclic moiety amethylene group may optionally be replaced by an —N(R^(8c)) group, anoxygen or sulphur atom or a —S(O) or —S(O)₂ group, or wherein in 4- to7-membered cyclic groups in the cyclic moiety two adjacent methylenegroups together may optionally be replaced by a —C(O)N(R^(8b)) or—S(O)₂N(R^(8b)) group, or wherein in 6- to 7-membered cyclic groups inthe cyclic moiety three adjacent methylene groups together mayoptionally be replaced by a substituted —OC(O)N(R^(8b)) or—N(R^(8b))C(O)N(R^(8b)) or —N(R^(8b))S(O)₂N(R^(8b)) group, with theproviso that a 3- to 7-membered cycloalkyl, cycloalkyl-C₁₋₅-alkyl orcycloalkyleneimino-C₂₋₃-alkyl group as hereinbefore defined wherein twoheteroatoms from the group comprising oxygen and nitrogen are separatedfrom one another by precisely one optionally substituted —CH₂ group, isexcluded, while a 3- to 7-membered cycloalkyl, cycloalkyl-C₁₋₅-alkyl orcycloalkyleneimino-C₂₋₃-alkyl group as hereinbefore defined may besubstituted at one or two —CH₂ groups by one or two C₁₋₃-alkyl groups ineach case, B denotes a group of the formula

Y denotes a nitrogen atom or a CH group, R⁶ denotes a hydrogen, ahalogen atom, an ethynyl, a methyl group, a methoxy group, while thehydrogen atoms of the methoxy group may optionally be wholly or partlyreplaced by fluorine atoms, while, unless otherwise stated, by the term“heteroaryl group” mentioned hereinbefore in the definitions is meant amonocyclic 5- or 6-membered heteroaryl group, while the 6-memberedheteroaryl group contains one, two or three nitrogen atoms and the5-membered heteroaryl group contains an imino group optionallysubstituted by a C₁₋₃-alkyl, phenyl or phenyl-C₁₋₃-alkyl group, anoxygen or sulphur atom or an imino group optionally substituted by aC₁₋₃-alkyl, phenyl, amino-C₂₋₃-alkyl, C₁₋₃-alkylamino-C₂₋₃-alkyl,di-(C₁₋₃-alkyl)-amino-C₂₋₃-alkyl, a C₃₋₆-cycloalkyleneimino-C₁₋₃-alkylor phenyl-C₁₋₃-alkyl group or an oxygen or sulphur atom and additionallya nitrogen atom or an imino group optionally substituted by a C₁₋₃-alkylor phenyl-C₁₋₃-alkyl group and two or three nitrogen atoms, and moreovera phenyl ring optionally substituted by a fluorine, chlorine or bromineatom, a C₁₋₃-alkyl, hydroxy, C₁₋₃-alkyloxy group, amino,C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino or C₃₋₆-cycloalkyleneimino groupmay be fused to the above-mentioned monocyclic heteroaryl groups via twoadjacent carbon atoms and the bond is effected via a nitrogen atom or acarbon atom of the heterocyclic moiety or a fused-on phenyl ring, while,unless otherwise stated, by the term “halogen atom” mentionedhereinbefore in the definitions is meant an atom selected from amongfluorine, chlorine, bromine and iodine, while the alkyl, alkenyl,alkynyl and alkoxy groups contained in the above-mentioned definitionswhich have more than two carbon atoms, unless otherwise stated, may bestraight-chain or branched and the alkyl groups in the previouslymentioned dialkylated groups, for example the dialkylamino groups, maybe identical or different, and the hydrogen atoms of the methyl or ethylgroups contained in the foregoing definitions, unless otherwise stated,may be wholly or partly replaced by fluorine atoms, or a tautomer orsalt thereof.
 4. A compound of the formula I according to claim 1,wherein, A denotes a group of the formula

wherein m is the number 1 or 2, R^(8a) each independently of one anotherdenote a hydrogen or fluorine atom or a C₁₋₃-alkyl, hydroxy,hydroxy-C₁₋₃-alkyl, C₁₋₃-alkoxy, C₁₋₃-alkoxy-C₁₋₃-alkyl, amino,C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino, amino-C₁₋₃-alkyl,C₁₋₃-alkylamino-C₁₋₃-alkyl, or di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl group,while in the previously mentioned substituted 5- to 7-membered groups Athe heteroatoms F, O or N optionally introduced with R^(8a) assubstituents are not separated by precisely one carbon atom from aheteroatom selected from among N, O and S, R^(8b) each independently ofone another denote a hydrogen atom or a C₁₋₃-alkyl group, R^(8c) eachindependently of one another denote a hydrogen atom, a C₁₋₃-alkyl,C₁₋₃-alkylcarbonyl, C₁₋₃-alkyloxycarbonyl or C₁₋₃-alkylsulphonyl group,X¹ denotes a carbonyl, or sulphonyl group, X² denotes an oxygen atom oran —NR^(8b) group, X³ denotes a carbonyl, thiocarbonyl, C═NR^(8c),C═N—OR^(8c), C═N—NO₂, C═N—CN or sulphonyl group, X⁴ denotes an oxygen orsulphur atom or an —NR^(8c) group, X⁵ denotes an oxygen atom or a —CH₂,—CHR^(8a) or —NR^(8c) group, R¹ denotes a hydrogen or halogen atom, aC₁₋₃-alkyl or C₁₋₃-alkoxy group, while the hydrogen atoms of theC₁₋₃-alkyl or C₁₋₃-alkoxy group may optionally be wholly or partlyreplaced by fluorine atoms, a C₂₋₃-alkenyl, C₂₋₃-alkynyl, nitrile, nitroor amino group, R² denotes a hydrogen or fluorine atom or a methylgroup, X denotes a nitrogen atom or a CH group, R³ denotes a hydrogenatom or a C₁₋₃-alkyl group, R⁴ denotes a hydrogen atom, a straight-chainor branched C₁₋₄-alkyl group, while the hydrogen atoms of thestraight-chain or branched C₁₋₄-alkyl group may optionally be wholly orpartly replaced by fluorine atoms, and which may optionally besubstituted by a C₁₋₃-alkyloxy group, while the hydrogen atoms of theC₁₋₃-alkyloxy group may optionally be wholly or partly replaced byfluorine atoms, R⁵ denotes a hydrogen atom, a hydroxy group, a OR⁹group, a C₂₋₄-alkenyl or C₂₋₄-alkynyl group, a straight-chain orbranched C₁₋₄-alkyl group, while the hydrogen atoms of thestraight-chain or branched C₁₋₄-alkyl group may optionally be wholly orpartly replaced by fluorine atoms, and which may optionally besubstituted by a C₃₋₅-cycloalkyl group, a nitrile, hydroxy, aC₁₋₅-alkyloxy group, while the hydrogen atoms of the C₁₋₅-alkyloxy groupmay optionally be wholly or partly replaced by fluorine atoms, anallyloxy, propargyloxy, benzyloxy, C₁₋₅-alkylcarbonyloxy,C₁₋₅-alkyloxycarbonyloxy, carboxy-C₁₋₅-alkyloxy,C₁₋₅-alkyloxycarbonyl-C₁₋₅-alkyloxy, mercapto, C₁₋₅-alkylsulphanyl,C₁₋₅-alkylsulphonyl, carboxy, C₁₋₅-alkyloxycarbonyl, aminocarbonyl,C₁₋₅-alkylaminocarbonyl, di-(C₁₋₅-alkyl)-aminocarbonyl,C₃₋₆-cycloalkyleneiminocarbonyl, aminosulphonyl,C₁₋₅-alkylaminosulphonyl, di-(C₁₋₅-alkyl)-aminosulphonyl,C₃₋₆-cycloalkyleneiminosulphonyl, amino, C₁₋₅-alkylamino,di-(C₁₋₅-alkyl)-amino, C₁₋₅-alkylcarbonylamino,C₁₋₅-alkyl-sulphonylamino, N-(C₁₋₅-alkylsulphonyl)-C₁₋₅-alkylamino orC₃₋₆-cycloalkylcarbonylamino group, while the 6- to 7-membered cyclicgroups of the C₃₋₆-cycloalkyleneiminocarbonyl group in the cyclic moietya methylene group in the 4 position of a 6- or 7-memberedcycloalkyleneimino group may be replaced by an oxygen or sulphur atom,by a carbonyl, sulphinyl, sulphonyl or —NR^(8c) group and additionally amethylene group adjacent to an above-mentioned —NR^(8c) group may bereplaced by a carbonyl group, a phenyl, heteroaryl, phenyl-C₁₋₅-alkyl orheteroaryl-C₁₋₅-alkyl group, which may optionally be mono- totrisubstituted in the phenyl or heteroaryl moiety may be substituted byidentical or different substituents selected from among halogen atoms,C₁₋₅-alkyl, di-(C₁₋₅-alkyl)-amino, hydroxy, C₁₋₅-alkyloxy, mono-, di- ortrifluoromethoxy, carboxy- and C₁₋₅-alkyloxycarbonyl groups, R⁹ denotesa straight-chain or branched C₁₋₄-alkyl group, while the hydrogen atomsof the straight-chain or branched C₁₋₄-alkyl group may optionally bewholly or partly replaced by fluorine atoms, and which may optionally besubstituted by a C₃₋₅-cycloalkyl group, a hydroxy, a C₁₋₅-alkyloxygroup, while the hydrogen atoms of the C₁₋₅-alkyloxy group mayoptionally be wholly or partly replaced by fluorine atoms, an allyloxy,propargyloxy, benzyloxy, C₁₋₅-alkylcarbonyloxy,C₁₋₅-alkyloxycarbonyloxy, carboxy-C₁₋₅-alkyloxy,C₁₋₅-alkyloxycarbonyl-C₁₋₅-alkyloxy, carboxy, C₁₋₅-alkyloxycarbonyl,aminocarbonyl, C₁₋₅-alkylaminocarbonyl, di-(C₁₋₅-alkyl)-aminocarbonyl,C₃₋₆-cycloalkyleneiminocarbonyl, amino, C₁₋₅-alkylamino,di-(C₁₋₅-alkyl)-amino, C₁₋₅-alkylcarbonylamino,C₁₋₅-alkylsulphonylamino, N-(C₁₋₅-alkylsulphonyl)-C₁₋₅-alkylamino orC₃₋₆-cycloalkylcarbonylamino group, while the 6- to 7-membered cyclicgroups of the C₃₋₆-cycloalkyleneiminocarbonyl group in the cyclic moietya methylene group in the 4 position of a 6- or 7-memberedcycloalkyleneimino group may be replaced by an oxygen or sulphur atom,by a carbonyl, sulphinyl, sulphonyl or —NR^(8c) group and additionally amethylene group adjacent to an above-mentioned —NR^(8c) group may bereplaced by a carbonyl group, with the proviso that the replacement ofhydrogen atoms of the first carbon atom of the straight-chain orbranched C₁₋₄-alkyl group by substituents from the group comprisingoxygen, sulphur or nitrogen is excluded, a phenyl or heteroaryl groupwhich may optionally be mono- to trisubstituted in the phenyl orheteroaryl moiety by identical or different substituents selected fromamong halogen atoms, C₁₋₅-alkyl, di-(C₁₋₅-alkyl)-amino, hydroxy,C₁₋₅-alkyloxy, mono-, di- or trifluoromethoxy, carboxy- andC₁₋₅-alkyloxycarbonyl groups, a phenyl-C₁₋₅-alkyl orheteroaryl-C₁₋₅-alkyl group, which may optionally be mono- totrisubstituted in the phenyl or heteroaryl moiety by identical ordifferent substituents selected from among halogen atoms, C₁₋₅-alkyl,di-(C₁₋₅-alkyl)-amino, hydroxy, C₁₋₅-alkyloxy, mono-, di- ortrifluoromethoxy, carboxy- and C₁₋₅-alkyloxycarbonyl groups, and whichmay optionally be substituted in the C₁₋₅-alkyl-moiety by a hydroxy, aC₁₋₅-alkyloxy group, while the hydrogen atoms of the C₁₋₅-alkyloxy groupmay optionally be wholly or partly replaced by fluorine atoms, anallyloxy, propargyloxy, benzyloxy, C₁₋₅-alkylcarbonyloxy,C₁₋₅-alkyloxycarbonyloxy, carboxy-C₁₋₅-alkyloxy, or aC₁₋₅-alkyloxycarbonyl-C₁₋₅-alkyloxy group; B denotes a group of theformula

Y denotes a nitrogen atom or a CH group, R⁶ denotes a hydrogen, ahalogen atom, an ethynyl, a methyl group, a methoxy group, while thehydrogen atoms of the methoxy group may optionally be wholly or partlyreplaced by fluorine atoms, while, unless otherwise stated, by the term“heteroaryl group” mentioned hereinbefore in the definitions is meant amonocyclic 5- or 6-membered heteroaryl group, while the 6-memberedheteroaryl group contains one, two or three nitrogen atoms and the5-membered heteroaryl group contains an imino group optionallysubstituted by a C₁₋₃-alkyl, phenyl or phenyl-C₁₋₃-alkyl group, or anoxygen or sulphur atom or an imino group optionally substituted by aC₁₋₃-alkyl, phenyl, amino-C₂₋₃-alkyl, C₁₋₃-alkylamino-C₂₋₃-alkyl,di-(C₁₋₃-alkyl)-amino-C₂₋₃-alkyl, a C₃₋₆-cycloalkyleneimino-C₁₋₃-alkylor phenyl-C₁₋₃-alkyl group, or an oxygen or sulphur atom andadditionally a nitrogen atom or an imino group optionally substituted bya C₁₋₃-alkyl or phenyl-C₁₋₃-alkyl group and two or three nitrogen atoms,and moreover a phenyl ring optionally substituted by a fluorine,chlorine or bromine atom, a C₁₋₃-alkyl, hydroxy, C₁₋₃-alkyloxy group,amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino or C₃₋₆-cycloalkyleneiminogroup may be fused to the above-mentioned monocyclic heteroaryl groupsvia two adjacent carbon atoms and the bond is effected via a nitrogenatom or a carbon atom of the heterocyclic moiety or a fused-on phenylring, while, unless otherwise stated, by the term “halogen atom”mentioned hereinbefore in the definitions is meant an atom selected fromamong fluorine, chlorine, bromine and iodine, while the alkyl, alkenyl,alkynyl and alkoxy groups contained in the above-mentioned definitionswhich have more than two carbon atoms, unless otherwise stated, may bestraight-chain or branched and the alkyl groups in the previouslymentioned dialkylated groups, for example the dialkylamino groups, maybe identical or different, and the hydrogen atoms of the methyl or ethylgroups contained in the foregoing definitions, unless otherwise stated,may be wholly or partly replaced by fluorine atoms, or a tautomer orsalt thereof.
 5. A compound of the formula I according to claim 1,wherein, A denotes a group of the formula

wherein m is the number 1 or 2, R^(8a) each independently of one anotherdenote a hydrogen or fluorine atom or a C₁₋₃-alkyl, hydroxy,hydroxy-C₁₋₃-alkyl, C₁₋₃-alkoxy, C₁₋₃-alkoxy-C₁₋₃-alkyl, amino,C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino, amino-C₁₋₃-alkyl,C₁₋₃-alkylamino-C₁₋₃-alkyl, or di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl group,while in the previously mentioned substituted 5- to 7-membered groups Athe heteroatoms F, O or N optionally introduced with R^(8a) assubstituents are not separated by precisely one carbon atom from aheteroatom selected from among N, O and S, R^(8b) each independently ofone another denote a hydrogen atom or a C₁₋₃-alkyl group, R^(8c) eachindependently of one another denote a hydrogen atom, a C₁₋₃-alkyl,C₁₋₃-alkylcarbonyl, C₁₋₃-alkyloxycarbonyl or C₁₋₃-alkylsulphonyl group,X¹ denotes a carbonyl or sulphonyl group, X² denotes an oxygen atom oran —NR^(8b) group, X³ denotes a carbonyl, thiocarbonyl, C═NR^(8c),C═N—OR^(8c), C═N—NO₂, C═N—CN or sulphonyl group, X⁴ denotes an oxygen orsulphur atom or an —NR^(8c) group, R¹ denotes a hydrogen, fluorine,chlorine or bromine atom, a methyl or methoxy group, while the hydrogenatoms of the methyl or methoxy group may optionally be wholly or partlyreplaced by fluorine atoms, R² denotes a hydrogen or fluorine atom, Xdenotes a nitrogen atom or a CH group, R³ denotes a hydrogen atom or aC₁₋₃-alkyl group, R⁴ denotes a hydrogen atom, R⁵ denotes a hydrogenatom, a hydroxy group, a OR⁹ group, a C₂₋₄-alkenyl or C₂₋₄-alkynylgroup, a straight-chain or branched C₁₋₄-alkyl group, while the hydrogenatoms may optionally be wholly or partly replaced by fluorine atoms, andwhich may optionally be substituted by a hydroxy, a C₁₋₃-alkyloxy group,while the hydrogen atoms of the C₁₋₃-alkyloxy group may be wholly orpartly replaced by fluorine atoms, a benzyloxy, C₁₋₃-alkylcarbonyloxy,C₁₋₃-alkyloxycarbonyl, aminocarbonyl, C₁₋₃-alkylaminocarbonyl,di-(C₁₋₃-alkyl)-aminocarbonyl, C₃₋₆-cycloalkyleneiminocarbonyl, amino,C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino, C₁₋₃-alkylcarbonylamino, orC₁₋₃-alkylsulphonylamino group, a phenyl, or C-linked heteroaryl group,while the heteroaryl group is selected from among pyrrolyl, oxazolyl,imidazolyl, furanyl, thiophenyl, thiazolyl, 1,2,3-triazolyl,1,2,4-triazolyl, tetrazolyl, pyridinyl, pyrimidinyl and pyrazinyl, andwhich may optionally be mono- to disubstituted in the heteroaryl moietyby identical or different substituents selected from among halogenatoms, C₁₋₃-alkyl, hydroxy, a C₁₋₃-alkyloxy, mono-, di- andtrifluoromethoxy groups, a phenyl-C₁₋₃-alkyl, heteroaryl-C₁₋₃-alkyl-group, while the heteroaryl group is selected from among pyrrolyl,oxazolyl, imidazolyl, furanyl, thiophenyl, thiazolyl, 1,2,3-triazolyl,1,2,4-triazolyl, tetrazolyl, pyridinyl, pyrimidinyl and pyrazinyl, andwhich may optionally be mono- to disubstituted in the heteroaryl moietyby identical or different substituents selected from among halogenatoms, C₁₋₃-alkyl, hydroxy, C₁₋₃-alkyloxy, mono-, di- andtrifluoromethoxy groups, and which may optionally be substituted in theC₁ ₃-alkyl moiety by a hydroxy, a C₁₋₃-alkyloxy group, while thehydrogen atoms of the C₁₋₃-alkyloxy group may optionally be wholly orpartly replaced by fluorine atoms, a C₁₋₅-alkylcarbonyloxy, or aC₁₋₅-alkyloxycarbonyloxy group; R⁹ denotes a straight-chain or branchedC₁₋₄-alkyl group, while the hydrogen atoms of the straight-chain orbranched C₁₋₄-alkyl group may optionally be wholly or partly replaced byfluorine atoms, and which may optionally be substituted by a hydroxy, aC₁₋₃-alkyloxy group, while the hydrogen atoms of the C₁₋₃-alkyloxy groupmay optionally be wholly or partly replaced by fluorine atoms, abenzyloxy, C₁₋₃-alkyloxycarbonyl, aminocarbonyl,C₁₋₃-alkylaminocarbonyl, di-(C₁₋₃-alkyl)-aminocarbonyl,C₃₋₆-cycloalkyleneiminocarbonyl, amino, C₁₋₃-alkylamino,di-(C₁₋₃-alkyl)-amino, C₁₋₃-alkylcarbonylamino, C₁₋₃-alkylsulphonylaminogroup, with the proviso that the replacement of hydrogen atoms of thefirst carbon atom of the straight-chain or branched C₁₋₄-alkyl group bysubstituents from the group comprising oxygen, sulphur or nitrogen isexcluded, a phenyl, phenyl-C₁₋₂-alkyl, heteroaryl-C₁₋₂-alkyl or C-linkedheteroaryl group while the heteroaryl group is selected from amongpyrrolyl, oxazolyl, imidazolyl, furanyl, thiophenyl, thiazolyl,1,2,3-triazolyl, 1,2,4-triazolyl, tetrazolyl, pyridinyl, pyrimidinyl andpyrazinyl, and which may optionally be mono- to disubstituted in theheteroaryl moiety by identical or different substituents selected fromamong halogen atoms, C₁₋₃-alkyl, hydroxy, C₁₋₃-alkyloxy, mono-, di- andtrifluoromethoxy groups, B denotes a group of general formula

R⁶ denotes a hydrogen, a chlorine or bromine atom, an ethynyl, a methylor a methoxy group, while, unless otherwise stated, by the term “halogenatom” mentioned hereinbefore in the definitions is meant an atomselected from among fluorine, chlorine, bromine and iodine, while thealkyl, alkenyl, alkynyl and alkoxy groups contained in theabove-mentioned definitions which have more than two carbon atoms,unless otherwise stated, may be straight-chain or branched and the alkylgroups in the previously mentioned dialkylated groups, for example thedialkylamino groups, may be identical or different, and the hydrogenatoms of the methyl or ethyl groups contained in the foregoingdefinitions, unless otherwise stated, may be wholly or partly replacedby fluorine atoms, or a tautomer or salt thereof.
 6. A compound of theformula I according to claim 1, wherein, A denotes a group of theformula

wherein m is the number 1 or 2, R^(8a) each independently of one anotherdenote a hydrogen or fluorine atom or a C₁₋₃-alkyl, hydroxy,hydroxy-C₁₋₃-alkyl, C₁₋₃-alkoxy, C₁₋₃-alkoxy-C₁₋₃-alkyl, amino,C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino, amino-C₁₋₃-alkyl,C₁₋₃-alkylamino-C₁₋₃-alkyl, or di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl group,while in the previously mentioned substituted 5- to 7-membered groups Athe heteroatoms F, O or N optionally introduced with R^(8a) assubstituents are not separated by precisely one carbon atom from aheteroatom selected from among N, O and S, R^(8b) each independently ofone another denote a hydrogen atom or a C₁₋₃-alkyl group, R^(8c) eachindependently of one another denote a hydrogen atom, a C₁₋₃-alkyl,C₁₋₃-alkylcarbonyl, C₁₋₃-alkyloxycarbonyl or C₁₋₃-alkylsulphonyl group,X¹ denotes a carbonyl or sulphonyl group, X² denotes an oxygen atom oran —NR^(8b) group, X³ denotes a carbonyl or sulphonyl group, X⁴ denotesan oxygen atom or an —NR^(8c) group, R¹ denotes a hydrogen, fluorine,chlorine or bromine atom, a methyl, trifluoromethyl or methoxy group, R²denotes a hydrogen atom, X denotes a nitrogen atom or a CH group, R³denotes a hydrogen atom or a methyl group, R⁴ denotes a hydrogen atom,R⁵ denotes a hydrogen atom, a hydroxy group, a OR⁹ group, an allyl ormethallyl group, a methyl group which may optionally be substitutedindependently of one another by a C₁₋₃-alkyl, hydroxy, OR⁹ group,aminocarbonyl, pyridin-4-yl, pyridin-3-yl, pyridin-2-yl, pyrazin-2-yl,pyrazin-3-yl or phenyl group, a phenyl group, R⁹ a straight-chain orbranched C₁₋₄-alkyl group, which may optionally be substituted by ahydroxy, a C₁₋₃-alkoxy group, a benzyloxy or a di-(C₁₋₃-alkyl)-aminogroup, with the proviso that the replacement of hydrogen atoms of thefirst carbon atom of the straight-chain or branched C₁₋₄-alkyl group bysubstituents from the group comprising oxygen or nitrogen is excluded, Bdenotes a group of general formula

R⁶ denotes a chlorine or bromine atom or an ethynyl group, while, unlessotherwise stated, by the term “halogen atom” mentioned hereinbefore inthe definitions is meant an atom selected from among fluorine, chlorine,bromine and iodine, while the alkyl, alkenyl, alkynyl and alkoxy groupscontained in the above-mentioned definitions which have more than twocarbon atoms, unless otherwise stated, may be straight-chain or branchedand the alkyl groups in the previously mentioned dialkylated groups, forexample the dialkylamino groups, may be identical or different, and thehydrogen atoms of the methyl or ethyl groups contained in the foregoingdefinitions, unless otherwise stated, may be wholly or partly replacedby fluorine atoms, or a tautomer or salt thereof.
 7. A compound of theformula I according to claim 1 wherein, the group B denotes the group

or a tautomer or salt thereof.
 8. A compound of the formula I accordingto claim 1 wherein, the group B denotes the group

or a tautomer or salt thereof.
 9. A compound selected from the groupconsisting of the following: (1) 5-bromo-thiophene-2-carboxylicacid-{1-[3-chloro-4-(2-oxo-[1,3]oxazinan-3-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide(2) 5-chloro-thiophene-2-carboxylicacid-{1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide(3) 5-chloro-thiophene-2-carboxylicacid-{1-[3-chloro-4-(2-oxo-[1,3]oxazinan-3-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide(4) (R)-5-bromo-thiophene-2-carboxylicacid-{1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide(5) (R)-5-bromo-thiophene-2-carboxylicacid-{5-oxo-1-[5-(3-oxo-morpholin-4-yl)-pyridin-2-yl]-pyrrolidin-3-yl}-amide (6)5-bromo-thiophene-2-carboxylic acid-{(3R,4R)-4-methyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide(7) (R)-5-bromo-thiophene-2-carboxylicacid-{1-[2,5-difluoro-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide(8) 5-bromo-thiophene-2-carboxylicacid-{1-[3-methyl-4-(5-oxo-[1,4]oxazepan-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide(9)(R)-5-ethynyl-thiophene-2-carboxylicacid-{1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide(10) 5-ethynyl-thiophene-2-carboxylicacid-{1-[3-methyl-4-(5-oxo-[1,4]oxazepan-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide(11) 5-bromo-thiophene-2-carboxylicacid-{1-[3-methyl-4-(2-oxo-[1,3]oxazepan-3-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide(12) 5-ethynyl-thiophene-2-carboxylicacid-{(3R,4R)-4-methyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide (13)(R)-5-bromo-thiophene-2-carboxylicacid-{1-[6-methyl-5-(3-oxo-morpholin-4-yl)-pyridin-2-yl]-5-oxo-pyrroldin-3-yl}-amide(14) (R)-5-bromo-thiophene-2-carboxylicacid-{1-[4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrroldin-3-yl}-amide(15) (R)-5-ethynyl-thiophene-2-carboxylicacid-{5-oxo-1-[6-methyl-5-(3-oxo-morpholin-4-yl)-pyridin-2-yl]-pyrrolidin-3-yl}-amide (16)(R)-5-chloro-thiophene-2-carboxylicacid-{1-[6-methyl-5-(3-oxo-morpholin-4-yl)-pyridin-2-yl]-5-oxo-pyrroldin-3-yl}-amide(17) (R)-5-ethynyl-thiophene-2-carboxylicacid-{5-oxo-1-[4-(3-oxo-morpholin-4-yl)-phenyl]-pyrrolidin-3-yl}-amide(18) (R)-5-chloro-thiophene-2-carboxylicacid-{5-oxo-1-[4-(3-oxo-morpholin-4-yl )-phenyl]-pyrrolidin-3-yl}-amide(19) (R)-4-bromo-thiophene-2-carboxylicacid-{1-[5-oxo-4-(3-oxo-morpholin-4-yl)- phenyl]-pyrrolidin-3-yl}-amide(20) (R)-5-bromo-thiophene-2-carboxylicacid-{5-oxo-1-[4-(2-oxo-piperidin-1-yl )-phenyl]-pyrrolidin-3-yl}-amide(21) (R)-5-ethynyl-thiophene-2-carboxylicacid-{5-oxo-1-[4-(2-oxo-piperidin-1-yl)-phenyl]-pyrrolidin-3-yl}-amide(22) (R)-5-bromo-thiophene-2-carboxylicacid-{5-oxo-1-[4-(3-oxo-morpholin-4-yl)-3-trifluoromethyl-phenyl]-pyrrolidin-3-yl}-amide (23)(R)-4-bromo-thiophene-2-carboxylicacid-{1-[3-methyl-4-(3-oxo-[1,4]oxazepan-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide(24) 5-ethynyl-thiophene-2-carboxylicacid-{1-[3-methyl-4-(5-oxo-[1,4]oxazepan-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide(25) 5-chloro-thiophene-2-carboxylicacid-{1-[3-chloro-4-(2-oxo-azepan-1-yl)-phenyl]-5-oxo-pyrroldin-3-yl}-amide(26) 5-bromo-thiophene-2-carboxylicacid-{(3R,4S)-4-hydroxy-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide(27) 5-bromo-thiophene-2-carboxylicacid-{4-methoxy-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide,(28) 5-ethynyl-thiophene-2-carboxylicacid-{4-methoxy-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide,(29) 5-bromo-thiophene-2-carboxylicacid-{4-methoxy-1-[3-chloro-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide,(30) 5-bromo-thiophene-2-carboxylicacid-{4-methoxy-1-[4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide,(31) 5-bromo-thiophene-2-carboxylicacid-{1-[3-chloro-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-4-pyridin-3-ylmethyl-pyrroldin-3-yl}-amide (32) 5-bromo-thiophene-2-carboxylicacid-{4-carbamoylmethyl-5-oxo-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-pyrrolidin-3-yl}-amide(33) 5-bromo-thiophene-2-carboxylicacid-{4-methyl-5-oxo-1-[4-(3-oxo-morpholin-4-yl)-phenyl]-pyrrolidin-3-yl}-amide(34) 5-bromo-thiophene-2-carboxylicacid-{4-methyl-1-[6-methyl-5-(3-oxo-morpholin-4-yl)-pyridin-2-yl]-5-oxo-pyrroldin-3-yl}-amide (35)5-bromo-thiophene-2-carboxylic acid-{4-dimethylaminocarbamoylmethyl-3-methyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide,(36) (R)-5-bromo-thiophene-2-carboxylicacid-{1-[3-chloro-4-(5-oxo-[1,4]oxazepan-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide(37) (R)-5-chloro-thiophene-2-carboxylic acid-{1-[3-methyl-4-(5-oxo-[1,4]oxazepan-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide(38) (R)-5-bromo-thiophene-2-carboxylicacid-{4-methoxy-1-[3-methyl-4-(5-oxo-[1,4]oxazepan-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide(39) (R)-5-bromo-thiophene-2-carboxylic acid-{4-hydroxy-1-[3-methyl-4-(5-oxo-[1,4]oxazepan-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide(40) 5-bromo-thiophene-2-carboxylicacid-{4-ethoxy-1-[3-methyl-4-(5-oxo-[1,4]oxazepan-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide(41) 5-ethynyl-thiophene-2-carboxylic acid-{4-methoxy-1-[3-methyl-4-(5-oxo-[1,4]oxazepan-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide(42) 5-bromo-thiophene-2-carboxylic acid-{4-(2-methoxy-ethoxy)-1-[3-methyl-4-(5-oxo-[1,4]oxazepan-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide(43) 5-bromo-thiophene-2-carboxylicacid-{4-hydroxymethyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide(44) 5-bromo-thiophene-2-carboxylicacid-{4-methoxymethyl-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide,and (45) 5-bromo-th iophene-2-carboxylic acid-{4-(2-hydroxy-ethyl)-1-[3-methyl-4-(3-oxo-morpholin-4-yl)-phenyl]-5-oxo-pyrrolidin-3-yl}-amide,or a tautomer or salt thereof.
 10. A physiologically acceptable salt ofa compound according to one of claims 1 to
 9. 11. A pharmaceuticalcomposition containing a compound according to one of claims 1 to 9 or aphysiologically acceptable salt thereof together with one or more inertcarriers and/or diluents.